Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Psychiatry
Secondary Appointment(s):
Pediatrics, Pharmacology
Location:
MPRC, 3-6
Phone (Primary):
(410) 402-7635
Phone (Secondary):
(443) 851-3332 (cell)
Education and Training
1968: B.Sc. in Chemistry, University of Vienna, Austria
1974: Ph.D. in Biochemistry, University of Vienna, Austria
1975 - 1977: Postdoctoral Fellow with J.T. Coyle, M.D., Department of Pharmacology, Johns Hopkins University, Baltimore, Maryland, USA
1977 - 1979: Postdoctoral Fellow with K. Fuxe, M.D., Department of Histology, Karolinska Institute, Stockholm, Sweden
Biosketch
NAME: SCHWARCZ, ROBERT
eRA COMMONS USER NAME (credential, e.g., agency login): SCHWARCZ
POSITION TITLE: Professor of Psychiatry, Pharmacology and Pediatrics
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
| INSTITUTION AND LOCATION | DEGREE (if applicable) | Completion Date MM/YYYY | FIELD OF STUDY |
| University of Vienna | PhD | 1974 | Biochemistry |
| Johns Hopkins University | Postdoctoral Fellow | 1977 | Neuropharmacology |
| Karolinska Institute | Postdoctoral Fellow | 1979 | Histology |
A. PERSONAL STATEMENT
During the past 35+ years, most of the work in the laboratory has been concerned with the neurobiology of quinolinate (QUIN) and kynurenate (KYNA), two metabolically related brain constituents with neuroexcitatory (and excitotoxic) and neuroinhibitory (and neuroprotective) properties, respectively. Both QUIN and KYNA are products of the kynurenine pathway of tryptophan degradation. Using a combination of biochemical, histological, behavioral and electrophysiological techniques, we have elaborated many of the characteristics and control mechanisms which govern the function of QUIN and KYNA in the brain. Ongoing in vivo and in vitro studies are designed 1) to identify possible abnormalities in kynurenine pathway metabolism in major neurological and psychiatric diseases, and in relevant animal models; 2) to further define the neurobiology of QUIN and KYNA in animals by manipulating the kynurenine pathway pharmacologically and genetically; and 3) to develop and use novel kynurenergic drugs in order to normalize functional impairments in the central nervous system. My laboratory currently consists of 8 team members (senior/postdoctoral scientists, students and research assistants), who focus mainly on work with experimental animals and on studies with clinical samples provided by investigators at my own institution and by selected external collaborators.
B. Positions and Honors
Positions and Employment
1979 - 1982 Assistant Professor of Psychiatry, University of Maryland Baltimore, Maryland Psychiatric
Research Center
1982 - 1986 Associate Professor of Psychiatry, University of Maryland Baltimore, Maryland Psychiatric
Research Center
1986 - Professor of Psychiatry, University of Maryland Baltimore, Maryland Psychiatric Research
Center
Selected Honors
1994 Merck Neuroscience Lecturer, British Pharmacological Society
1998 4th Hillarp Lecture, Society for Neuroscience
2001 Dezsö Miskolczy Memorial Lecturer, University of Szeged, Hungary
2007 Regents' Faculty Award, University System of Maryland
2007 Epilepsy Research Award, ASPET
2009 Foreign Adjunct Professor, Karolinska Institute (elected)
2015 Musajo Medal, International Society for Tryptophan Research
Selected other Experience and Professional Memberships
1987 - 1993 Scientific Council, Huntington's Disease Society of America
1990 - 1994 Member, Neurological Sciences 2, NINDS Study Section
1988 Member, ACNP (Fellow, 2000)
2001 - 2003 and 2006 - 2008 Member, ACNP Program Committee
2007 Chair, ACNP Program Committee
2007 - 2008 Member, Program Committee, American Epilepsy Society
2007 - 2009 Member, Research Initiative Fund Review Committee, American Epilepsy Society
2008 - 2018 Member, Board of Trustees, Medical University of Vienna
2009 - Member, Scientific Council, Brain & Behavior Research Foundation (NARSAD)
2009 - 2011 Member, ACNP Liaison Commitee
2012 - 2014 Member, ACNP Ethics Committee
2016 - 2018 Member, ACNP Awards Committee
C. Contributions to science
1. During my postdoctoral period, first under the mentorship of Dr. Joseph Coyle (Johns Hopkins University), then with Drs. Kjell Fuxe and Tomas Hökfelt (Karolinska Institute), I was concerned mainly with the molecular and cellular mechanisms that underlie nerve cell death in the central nervous system. I showed that an intrastriatal injection of the excitatory amino acid kainate provides a faithful animal model for the neurodegenerative disorder Huntington's Disease. In Stockholm, I discovered that ibotenic acid, another excitatory amino acid receptor agonist, duplicates the selective toxic effects of kainate in the striatum. Compared to kainate, however, ibotenate turned out to be a superior experimental lesioning tool, which is being used to this day in neuroscience laboratories throughout the world. These studies with kainate and ibotenate led to the idea, widely confirmed and echoed during the past 35+ years, that "excitotoxic" processes, triggered by an overstimulation of excitatory amino acid receptors, are causally involved in the pathophysiology of several major neurological diseases.
a. Coyle JT, Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature. 1976 Sep 16;263(5574):244-6. PubMed PMID: 8731.
b. Schwarcz R, Creese I, Coyle JT, Snyder SH. Dopamine receptors localised on cerebral cortical afferents to rat corpus striatum. Nature. 1978 Feb 23;271(5647):766-8. PubMed PMID: 625348.
c. Schwarcz R, Fuxe K, Agnati LF, Hökfelt T, Coyle JT. Rotational behaviour in rats with unilateral striatal kainic acid lesions: a behavioural model for studies on intact dopamine receptors. Brain Res. 1979 Jul 20;170(3):485-95. PubMed PMID: 37986.
d. Schwarcz R, Hökfelt T, Fuxe K, Jonsson G, Goldstein M, Terenius L. Ibotenic acid-induced neuronal degeneration: a morphological and neurochemical study. Exp Brain Res. 1979. Oct ;37(2):199-216. PubMed PMID: 40808.
2. In the early 1980s, at the beginning of my career as an independent investigator, I developed the concept that antagonists of excitatory amino acid ("glutamate") receptors ought to prevent or arrest neurodegeneration and may thus hold promise as novel therapeutic agents for catastrophic brain diseases. I verified this idea in several relevant neurological disease models. In the following years, this breakthrough discovery led to the establishment of anti-excitotoxin-based drug development programs in most major pharmaceutical companies.
a. Schwarcz R, Collins JF, Parks DA. Alpha-amino-omega-phosphonocarboxylates block ibotenate but not kainate neurotoxicity in rat hippocampus. Neurosci Lett. 1982 Nov 16;33(1):85-90. PubMed PMID: 6130496.
b. Aldinio C, French ED, Schwarcz R. The effects of intrahippocampal ibotenic acid and their blockade by (-2-amino-7-phosphonoheptanoic acid: morphological and electroencephalographical analysis. Exp Brain Res. 1983;51(1):36-44. PubMed PMID: 6309547.
c. Schwarcz R, Collins J, Curry K., inventors. Aminoacid Isomers, Their Production and Their Medicinal Use. USA 4,483,853. 1984 November 20.
d. Schwarcz R, Meldrum B. Excitatory aminoacid antagonists provide a therapeutic approach to neurological disorders. Lancet. 1985 Jul 20;2(8447):140-3. PubMed PMID: 2862329.
3. Based on my hypothesis that endogenous excitotoxins may play a role in the pathophysiology of human brain disorders, I discovered, in 1983, that the tryptophan metabolite quinolinic acid (QUIN) triggers specific neurodegenerative events in the mammalian brain. I subsequently identified QUIN as a regular constituent of the human brain, described and characterized its metabolic enzymes in the brain and found, unexpectedly, that the metabolite was produced in, and released from, glial cells rather than neurons. This led me to propose in the 1980s, i.e. at a time when glial cells were still considered “brain glue” or at best suppliers of nutrition and energy to neurons, that glia-derived QUIN, by targeting glutamate receptors on nerve cells, may play an important role in neuronal function and dysfunction. My interest in the neurobiology of QUIN then prompted me to investigate the effects of a related tryptophan metabolite, kynurenic acid (KYNA). I first showed that KYNA exists normally in the mammalian brain and possesses pronounced neuroprotective and anticonvulsant properties. I then demonstrated that KYNA’s biosynthetic enzymes in the brain reside preferentially in astrocytes. Further characterization of KYNA metabolism revealed that one of these enzymes, which we named kynurenine aminotransferase (KAT) II, singularly controls the function of neuroactive KYNA.
a. Schwarcz R, Whetsell WO Jr, Mangano RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science. 1983 Jan 21;219(4582):316-8. PubMed PMID: 6849138.
b. Köhler C, Okuno E, Flood PR, Schwarcz R. Quinolinic acid phosphoribosyltransferase: preferential glial localization in the rat brain visualized by immunocytochemistry. Proc Natl Acad Sci USA. 1987 May;84(10):3491-5. PubMed PMID: 3472219; PMCID: PMC304897.
c. Turski WA, Gramsbergen JB, Trait ler H, Schwarcz R. Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine. J Neurochem. 1989 May;52(5):1629-36. PubMed PMID: 2709016.
d. Okuno E, Nakamura M, Schwarcz R. Two kynurenine aminotransferases in human brain. Brain Res. 1991 Mar 1;542(2):307-12. PubMed PMID: 2029638.
4. Using both genetic approaches and new pharmacological tools designed together with my postdocs, students and collaborators nationally and internationally, I went on to show that selective attenuation of KATII activity has profound effects on the fate and function of the classic neurotransmitters glutamate, dopamine, acetylcholine and – as shown more recently – GABA. Originating from astrocytes, KYNA is therefore a new, chemical messenger with unique neuromodulatory properties. This insight led me and others to propose a role of (fluctuations in) astrocyte-derived KYNA in the control of physiological processes ranging from neurotransmitter release and mechanisms involved in synapse formation and neuronal plasticity to motor and cognitive behaviors. Validation of this concept, in several cases using specific KAT II inhibitors first tested in my laboratory, has now been provided by distinguished scientists worldwide.
a. Rassoulpour A, Wu HQ, Ferre S, Schwarcz R. Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum. J Neurochem. 2005 May;93(3):762-5. PubMed PMID: 15836634.
b. Pellicciari R, Rizzo RC, Costantino G, Marinozzi M, Amori L, Guidetti P, Wu HQ, Schwarcz R. Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potentand selective kynurenine aminotransferase II (KATII) inhibitor. ChemMedChem. 2006 May;1(5):528-31. PubMed PMID: 16892388.
c. Potter MC, Elmer GI, Bergeron R, Albuquerque EX, Guidetti P, Wu HQ, Schwarcz R. Reduction of endogenous kynurenic acid formation enhances extracellular glutamate, hippocampal plasticity, and cognitive behavior. Neuropsychopharmacology. 2010 Jul;35(8):1734-42. PubMed PMID: 20336058; PubMed Central PMCID: PMC3055476.
d. Beggiato S, Tanganelli S, Fuxe K, Antonelli T, Schwarcz R, Ferraro L. Endogenous kynurenic acid regulates extracellular GABA levels in the rat prefrontal cortex. Neuropharmacology. 2014 Jul;82:11-8. PubMed PMID: 24607890.
5. During the past 15 years, it became clear that drugs which are able to normalize the balance between QUIN and KYNA in the brain hold great promise for the treatment of major human brain diseases, including Parkinson’s disease, Alzheimer’s disease, depressive disorders, schizophrenia and drug abuse. Depending on the nature of the underlying disease process, QUIN synthesis inhibitors or KATII inhibitors are currently considered prime candidates for clinical interventions. Our recent papers, as well as studies by other investigators in both academia and industry, attest to the feasibility of This new approach and have provided impressive proof-of-concept data in relevant disease models.
a. Zwilling D, Huang SY, Sathyasaikumar KV, Notarangelo FM, Guidetti P, Wu HQ, Lee J, Truong J, Andrews-Zwilling Y, Hsieh EW, Louie JY, Wu T, Scearce-Levie K, Patrick C, Adame A, Giorgini F, Moussaoui S, Laue G, Rassoulpour A, Flik G, Huang Y, Muchowski JM, Masliah E, Schwarcz R, Muchowski PJ. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell. 2011 Jun 10;145(6):863-74. PubMed PMID: 21640374; PubMed Central PMCID: PMC3118409.
b. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012 Jul;13(7):465-77. PubMed PMID: 22678511; PubMed Central PMCID: PMC3681811.
c. Justinova Z, Mascia P, Wu HQ, Secci ME, Redhi GH, Panlilio LV, Scherma M, Barnes C, Parashos A, Zara T, Fratta W, Solinas M, Pistis M, Bergman J, Kangas BD, Ferré S, Tanda G, Schwarcz R, Goldberg SR. Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nat Neurosci. 2013 Nov;16(11):1652-61. PubMed PMID: 24121737; PubMed Central PMCID: PMC3835353.
d. Wu HQ, Okuyama M, Kajii Y, Pocivavsek A, Bruno JP, Schwarcz R. Targeting kynurenine aminotransferase II in psychiatric diseases: promising effects of an orally active enzyme inhibitor. Schizophr Bull. 2014 Mar;40 Suppl 2:S152-8. PubMed PMID: 24562494; PubMed Central PMCID: PMC3934402.
Complete List of Published Work in My Bibliography: http://www.ncbi.nlm.nih.gov/myncbi/robert.schwarcz.1/bibliography/47299289/public/?sort=date&direction=ascending
Research/Clinical Keywords
Cognition, Excitotoxicity, Glutamate, Kynurenic acid, Neurodegenerative diseases, Neuroprotection, Quinolinic acid, Schizophrenia, Tryptophan
Highlighted Publications
Total: 332 Peer-reviewed Publications, 66 Book chapters
24,657 Citations
h-Factor: 91
5 most highly cited publications:
J.T. Coyle and R. Schwarcz: Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea. Nature, 263, 244-246 (1976)
R. Schwarcz, W.O. Whetsell Jr. and R.M. Mangano: Quinolinic acid: an endogenous metabolite that causes axon-sparing lesions in rat brain. Science, 219, 316-318 (1983)
R. Schwarcz and R. Pellicciari: Manipulation of brain kynurenines: glial targets, neuronal effects and clinical opportunities. J. Pharmacol. Exp. Therap., 303, 1-10 (2002)
C. Hilmas, E.F.R. Pereira, M. Alkondon, A. Rassoulpour, R. Schwarcz and E.X. Albuquerque: The brain metabolite kynurenic acid inhibits a7 nicotinic receptor activity and increases non-a7 nicotinic receptor expression: physiopathological implications. J. Neurosci., 21, 7463-7473 (2001)
R. Schwarcz, J.P. Bruno, P.J. Muchowski and H.-Q. Wu: Kynurenines in the mammalian brain: when physiology meets pathology. Nature Rev. Neurosci., 13, 465-477 (2012)
Additional Publication Citations
THESIS
R. Schwarcz: Zur Kenntnis der Biosynthese phosphorylierter Derivate des myo-Inosits in Hühnerblut. Ph.D. Dissertation, Universität Wien, 1974.
BOOKS/SPECIAL ISSUES EDITED
K. Fuxe, P.J. Roberts and R. Schwarcz (Editors): Excitotoxins. Macmillan, 363 pp., 1983.
R. Schwarcz and Y. Ben-Ari (Editors): Excitatory Amino Acids and Epilepsy. Plenum, 735 pp., 1986.
R. Schwarcz, S.N. Young and R.R. Brown (Editors): Kynurenine and Serotonin Pathways: Progress in Tryptophan Research. Plenum, 715 pp., 1991.
H.E. Scharfman, M. Witter and R. Schwarcz (Editors): The Parahippocampal Region: Implications for Neurological and Psychiatric Diseases. Annals of the New York Academy of Sciences, volume 911, 502 pp., 2000.
R. Schwarcz (Guest Editor): Glial Dysfunction in Epilepsy. Epilepsia Supplement, 2008.
R. Schwarcz (Editor): Neuropsychopharmacology: a Tribute to Joseph T. Coyle. Advances in Pharmacology, volume 76. Elsevier, 400 pp., 2016.
G. Clarke, T.W. Stone and R. Schwarcz (Guest Editors): The Kynurenine Pathway in Health and Disease. Neuropharmacology, volume 112, Part B, pp. 235-412, 2017.
ARTICLES IN PEER-REVIEWED JOURNALS
R. Schwarcz, W. Fried, F. Pittner and O. Hoffmann-Ostenhof: Anwendung der Affinitäts- chromatographie an NAD-Sepharose zum Nachweis und zur Reinigung von myo-Inosit-l-phosphat-Synthase in Erythrocyten von Hühnern und in Lemma gibba. Monatsh. f. Chemie, 105, 445-451 (1974).
J.T. Coyle and R. Schwarcz: Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea. Nature, 263, 244-246 (1976).
R. Schwarcz and J.T. Coyle: Adenylate cyclase activity in chick retina. Gen. Pharmacol., 7, 349-354 (1976).
R. Schwarcz and J.T. Coyle: Neurochemical sequelae of kainate injections in corpus striatum and substantia nigra of the rat. Life Sci., 20, 431-436 (1977).
R. Schwarcz and J.T. Coyle: Kainic acid: neurotoxic effects after intraocular injection. Invest. Ophthalmol. Vis. Sci., 16, 141-148 (1977).
R. Schwarcz, J.P. Bennett, Jr. and J.T. Coyle: Loss of striatal serotonin receptor binding induced by kainic acid lesions: correlations with Huntington's disease. J. Neurochem., 28, 867-869 (1977).
R. Schwarcz and J.T. Coyle: Striatal lesions with kainic acid: neurochemical characteristics. Brain Res., 127, 235-249 (1977).
R. Schwarcz, J.P. Bennett and J.T. Coyle: Inhibitors of GABA metabolism: implications for Huntington's disease. Ann. Neurol., 2, 299-303 (1977).
J.T. Coyle, R. Schwarcz, J.P. Bennett and P. Campochiaro: Clinical, neuropathologic and pharmacologic aspects of Huntington's disease: correlates with a new animal model. Progr. Neuro-Psychopharmacol., 1, 13-30 (1977).
P. Campochiaro, R. Schwarcz and J.T. Coyle: GABA-receptor binding in rat striatum: localization and effects of denervation. Brain Res., 136, 501-511 (1977).
R. Schwarcz, D. Scholz and J.T. Coyle: Structure-activity relations for the neurotoxicity of kainic acid derivatives and glutamate analogues. Neuropharmacology, 17, 145-151 (1978).
R. Schwarcz, I. Creese, J.T. Coyle and S.H. Snyder: Dopamine receptors localised on cerebral cortical afferents to rat corpus striatum. Nature, 271, 766-768 (1978).
R. Zaczek, R. Schwarcz and J.T. Coyle: Long-term sequelae of striatal kainate lesion. Brain Res., 152, 626-632 (1978).
R.E. Hruska, R. Schwarcz, J.T. Coyle and H.I. Yamamura: Alterations in muscarinic cholinergic receptors of the rat caudate nucleus after kainic acid injections. Brain Res., 152, 620-625 (1978).
R. Schwarcz, K. Fuxe, L.F. Agnati and J.-Å. Gustafsson: Effects of bromocriptine on 3H-spiroperidol binding sites in rat striatum. Evidence for actions of dopamine receptors not linked to adenylate cyclase. Life Sci., 23, 465-469 (1978).
R. Schwarcz, R. Zaczek and J.T. Coyle: Microinjection of kainic acid into rat hippocampus. Europ. J. Pharmacol., 50, 209-220 (1978).
W. Sieghart, J. Forn, R. Schwarcz, J.T. Coyle and P. Greengard: Evidence for neuronal localization of specific brain phosphoproteins. Brain Res., 156, 345-350 (1978).
C. Köhler, R. Schwarcz and K. Fuxe: Perforant path transections protect hippocampal granule cells from kainate lesion. Neurosci. Lett., 10, 241-246 (1978).
R. Schwarcz and K. Fuxe: 3H-Kainic acid binding: relevance for evaluating the neurotoxicity of kainic acid. Life Sci., 24, 1471-1480 (1979).
R. Schwarcz, K. Fuxe, L.F. Agnati, T. Hökfelt and J.T. Coyle: Rotational behavior in rats with unilateral striatal kainic acid lesions: a behavioral model for studies on intact dopamine receptors. Brain Res., 170, 485-495 (1979).
M.-L. Tjörnhammar, R. Schwarcz, T. Bartfai and K. Fuxe: Guanylate cyclase activity increases after kainic acid lesion of rat striatum. Brain Res., 171, 567-572 (1979).
C. Köhler, R. Schwarcz and K. Fuxe: Intrahippocampal injections of ibotenic acid provide histological evidence for a neurotoxic mechanism different from kainic acid. Neurosci. Lett., 15, 223-228 (1979).
C. Köhler, R. Schwarcz and K. Fuxe: Hippocampal lesions indicate differences between the excitotoxic properties of acidic amino acids. Brain Res., 175, 366-371 (1979).
R. Schwarcz, T. Hökfelt, K. Fuxe, G. Jonsson, M. Goldstein and L. Terenius: Ibotenic acid induced neuronal degeneration: a morphological and neurochemical study. Exp. Brain Res., 37, 199-216 (1979).
K. Andersson, R. Schwarcz and K. Fuxe: Compensatory bilateral changes in dopamine turnover after striatal kainate lesion. Nature, 283, 94-96 (1980).
R. Schwarcz, K. Fuxe, T. Hökfelt, L. Terenius and M. Goldstein: Effects of chronic striatal kainate lesions on some dopaminergic parameters and enkephalin immunoreactive neurons in the basal ganglia. J. Neurochem., 34, 772-778 (1980).
R. Schwarcz and C. Köhler: Evidence against an exclusive role of glutamate in kainic acid neurotoxicity. Neurosci. Lett., 19, 243-249 (1980).
R. Schwarcz: Effects of tissue storage and freezing on brain glutamate uptake. Life Sci., 28, 1147-1154 (1981).
R.M. Mangano and R. Schwarcz: The human platelet as a model for the glutamatergic neuron: platelet uptake of L-glutamate. J. Neurochem., 36, 1067-1076 (1981).
C. Köhler and R. Schwarcz: Monosodium glutamate: increased neurotoxicity after removal of neuronal re-uptake sites. Brain Res., 211, 485-491 (1981).
R.M. Mangano and R. Schwarcz: Platelet glutamate and aspartate uptake in Huntington's disease. J. Neurochem., 37, 1072-1074 (1981).
R.M. Mangano and R. Schwarcz: Huntington's disease: glutamate and aspartate metabolism in blood platelets. J. Neurol. Sci., 53, 489-500 (1982).
R. Schwarcz and W.O. Whetsell Jr.: Post-mortem high affinity glutamate uptake in human brain. Neuroscience, 7, 1771-1778 (1982).
E.D. French, C. Aldinio and R. Schwarcz: Intrahippocampal kainic acid, seizures and local neuronal degeneration: relationships assessed in unanesthetized rats. Neuroscience, 7, 2525-2536 (1982).
R. Schwarcz, J.F. Collins and D.A. Parks: α-Amino-w-phosphonocarboxylates block ibotenate but not kainate neurotoxicity in rat hippocampus. Neurosci. Lett., 33, 85-90 (1982).
R. Schwarcz, W.O. Whetsell Jr. and R.M. Mangano: Quinolinic acid: an endogenous metabolite that causes axon-sparing lesions in rat brain. Science, 219, 316-318 (1983).
R.M. Mangano and R. Schwarcz: Chronic infusion of endogenous excitatory amino acids into rat striatum and hippocampus. Brain Res. Bull., 10, 47-51 (1983).
C. Köhler and R. Schwarcz: Comparison of ibotenate and kainate neurotoxicity in rat brain: a histological study. Neuroscience, 8, 819-835 (1983).
C. Aldinio, E.D. French and R. Schwarcz: Effects of intrahippocampal ibotenic acid and their blockade by (-) 2-amino 7-phosphono-heptanoic acid: morphological and electroencephalographical analysis. Exp. Brain Res., 51, 36-44 (1983).
R. Schwarcz and C. Köhler: Differential vulnerability of central neurons to quinolinic acid. Neurosci. Lett., 38, 85-90 (1983).
A.C. Foster, J.F. Collins and R. Schwarcz: On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds. Neuropharmacology, 22,1331-1342 (1983).
W.O. Whetsell Jr. and R. Schwarcz: The organotypic tissue culture model of corticostriatal system used for examining amino acid neurotoxicity and its antagonism: studies of kainic acid, quinolinic acid and (-) 2-amino-7-phosphonoheptanoic acid. J. Neural Transm., Suppl. 19, 53-63 (1983).
M. Wolfensberger, U. Amsler, M. Cuénod, A.C. Foster, W.O. Whetsell Jr. and R. Schwarcz: Identification of quinolinic acid in rat and human brain tissues. Neurosci. Lett., 41, 247-252 (1983).
R. Schwarcz, A.C. Foster, E.D. French, W.O. Whetsell Jr. and C. Köhler: Excitotoxic models for neurodegenerative disorders. Life Sci., 35, 19-32 (1984).
R. Schwarcz, G.S. Brush, A.C. Foster and E.D. French: Seizure activity and lesions following intrahippocampal injection of quinolinic acid. Exp. Neurol., 84, 1-17 (1984).
A.C. Foster, L.P. Miller, W.H. Oldendorf and R. Schwarcz: Studies on the disposition of quinolinic acid after intracerebral or systemic administration in the rat. Exp. Neurol., 84, 428-440 (1984).
H.X. Steiner, G.J. McBean, C. Köhler, P.J. Roberts and R. Schwarcz: Ibotenate-induced neuronal degeneration in immature rat brain. Brain Res., 307, 117-124 (1984).
A.C. Foster, A. Vezzani, E.D. French and R. Schwarcz: Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci. Lett., 48, 273-278 (1984).
B.L. Gibson, R. Schwarcz and L. Reif-Lehrer: Quinolinate: a selective neurotoxin in embryonic and posthatching chicken retinas. Invest. Ophthalmol. Vis. Sci., 26, 50-57 (1985).
A.C. Foster, W.C. Zinkand and R. Schwarcz: Quinolinic acid phosphoribosyltransferase in rat brain. J. Neurochem., 44, 446-454 (1985).
A.C. Foster, W.O. Whetsell, Jr., E.D. Bird and R. Schwarcz: Quinolinic acid phosphoribosyltransferase in human and rat brain: activity in Huntington's disease and in quinolinate lesioned rat striatum. Brain Res., 336, 207-214 (1985).
A.C. Foster and R. Schwarcz: Characterization of quinolinic acid phosphoribosyltransferase in human blood and observations in Huntington's disease. J. Neurochem., 45, 199-205, (1985).
C. Aldinio, S. Mazzari, G. Toffano, C. Köhler and R. Schwarcz: Effects of intracerebral injections of quinolinic acid on serotonergic neurons in the rat brain. Brain Res., 341, 57-65 (1985).
C.B. Nemeroff, G.A. Mason, G. Bissette, D.A. Parks and R. Schwarcz: Effects of intrahypothalamic injection of quinolinic acid on anterior pituitary hormone secretion in the unanesthetized rat. Neuroendocrinology, 41, 332-336 (1985).
A. Vezzani, U. Ungerstedt, E.D. French and R. Schwarcz: In vivo brain dialysis of amino acids and simultaneous EEG measurements following intrahippocampal quinolinic acid injection: evidence for a dissociation between neurochemical changes and seizures. J. Neurochem., 45, 335-344 (1985).
E. Okuno and R. Schwarcz: Purification of quinolinic acid phosphoribosyltransferase from rat liver and brain. Biochim. Biophys. Acta, 841, 112-119 (1985).
R. Schwarcz and B. Meldrum: Excitatory amino acid antagonists provide a novel therapeutic approach to neurological disorders. Lancet, 2, 140-143 (1985).
A. Vezzani and R. Schwarcz: A noradrenergic component of quinolinic acid induced seizures. Exp. Neurol., 90, 254-258 (1985).
H. Björklund, L. Olson, D. Dahl and R. Schwarcz: Short-and long-term consequences of intracranial injections of the excitotoxin quinolinic acid as evidenced by GFA immunohistochemistry of astrocytes. Brain Res., 371, 267-277 (1986).
M. Goldstein, S. Kuga, N. Kusano, E. Meller, J. Dancis and R. Schwarcz: Dopamine agonist-induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brain stem: possible pharmacological model for Lesch-Nyhan syndrome. Brain Res., 367, 114-120 (1986).
A.C. Foster, R.J. White and R. Schwarcz: Synthesis of quinolinic acid by 3-hydroxyanthranilic acid oxygenase in rat brain tissue in vitro. J. Neurochem., 47, 23-30 (1986).
S. Mazzari, C. Aldinio, M. Beccaro, G. Toffano and R. Schwarcz: Intracerebral quinolinic acid injection in the rat: effects on dopaminergic neurons. Brain Res., 380, 309-316 (1986).
A.C. Foster, E. Okuno, D.S. Brougher and R. Schwarcz: A radioenzymatic assay for quinolinic acid. Anal. Biochem., 158, 98-103 (1986).
C. Köhler, E. Okuno, P.R. Flood and R. Schwarcz: Quinolinic acid phosphoribosyltransferase: preferential glial localization in the rat brain visualized by immunocytochemistry. Proc. Natl. Acad. Sci. (U.S.A.), 84, 3491-3495 (1987).
R. Schwarcz, C. Speciale and E.D. French: Hippocampal kynurenines as etiological factors in seizure disorders. Pol. J. Pharmacol. Pharm., 39, 485-494 (1987).
A. Vezzani, L. Sangalli, H.-Q. Wu and R. Schwarcz: ATP as a marker of excitotoxin-induced nerve cell death in vivo. J. Neural Transm., 70, 349-356 (1987).
E. Okuno, C. Köhler and R. Schwarcz: Rat 3-hydroxyanthranilic acid oxygenase: purification from the liver and immunocytochemical localization in the brain. J. Neurochem., 49, 771-780 (1987).
C. Speciale, E. Okuno and R. Schwarcz: Increased quinolinic acid metabolism following neuronal degeneration in the rat hippocampus. Brain Res., 436, 18-24 (1987).
C. Speciale and R. Schwarcz: Effect of systemic kainate administration on cerebral quinolinic acid metabolism in the rat. Exp. Neurol., 99, 213-218 (1988).
C. Köhler, A. Peterson, L.G. Eriksson, E. Okuno and R. Schwarcz: Immunohistochemical identification of quinolinic acid phosphoribosyltransferase in glial cultures from rat brain. Neurosci. Lett., 84, 115-119 (1988).
C. Köhler, L.G. Eriksson, P.R. Flood, J.A. Hardie, E. Okuno and R. Schwarcz: Quinolinic acid metabolism in the rat brain. Immunohistochemical identification of 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase in the hippocampal region. J. Neurosci., 8, 975-987 (1988).
E. Okuno, R.J. White and R. Schwarcz: Quinolinic acid phosphoribosyltransferase: purification and partial characterization from human liver and brain. J. Biochem., 103, 1054-1059 (1988).
R. Schwarcz, E. Okuno, R.J. White, E.D. Bird and W.O. Whetsell Jr.: 3-Hydroxyanthranilic acid oxygenase activity is increased in the brains of Huntington disease victims. Proc. Natl. Acad. Sci. (U.S.A.), 85, 4079-4081 (1988).
W.A. Turski, M. Nakamura, W.P. Todd, B.K. Carpenter, W.O. Whetsell Jr. and R. Schwarcz: Identification and quantification of kynurenic acid in human brain tissue. Brain Res., 454, 164-169 (1988).
C. Speciale, U. Ungerstedt and R. Schwarcz: Effect of kynurenine loading on quinolinic acid production in the rat: studies in vivo and in vitro. Life Sci., 43, 777-786 (1988).
W.A. Turski and R. Schwarcz: On the disposition of intrahippocampally injected kynurenic acid in the rat. Exp. Brain Res., 71, 563-567 (1988).
R. Schwarcz, C.A. Tamminga, R. Kurlan and I. Shoulson: Cerebrospinal fluid levels of quinolinic acid in Huntington's disease and schizophrenia. Ann. Neurol., 24, 580-582 (1988).
C. Köhler, L.G. Eriksson, E. Okuno and R. Schwarcz: Localization of quinolinic acid metabolizing enzymes in the rat brain. Immunohistochemical studies using antibodies to 3-hydroxyanthranilic acid oxygenase and quinolinic acid phosphoribosyltransferase. Neuroscience, 27, 49-76 (1988).
W.O. Whetsell, Jr. and R. Schwarcz: Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci. Lett., 97, 271-275 (1989).
W.A. Turski, J.B.P. Gramsbergen, H. Traitler and R. Schwarcz: Rat brain slices produce and liberate kynurenic acid upon exposure to L-kynurenine. J. Neurochem., 52, 1629-1636 (1989).
C. Speciale, K. Hares, R. Schwarcz and N. Brookes: High-affinity uptake of L-kynurenine by a Na+-independent transporter of neutral amino acids in astrocytes. J. Neurosci., 9, 2066-2072 (1989).
R. Schwarcz, E. Okuno and R.J. White: Basal ganglia lesions in the rat: effects on quinolinic acid metabolism. Brain Res., 490, 103-109 (1989).
W.P. Todd, B.K. Carpenter and R. Schwarcz: Preparation of 4-halo-3-hydroxyanthranilates and demonstration of their inhibition of 3-hydroxyanthranilate oxygenase in rat and human brain tissue. Prep. Biochem., 19, 155-165 (1989).
C. Speciale, U. Ungerstedt and R. Schwarcz: Production of extracellular quinolinic acid in the striatum studied by microdialysis in unanesthetized rats. Neurosci. Lett., 104, 345-350 (1989).
R. Schwarcz: Excitotoxic and anti-excitotoxic mechanisms in neurological disease. Curr. Opin. Neurol. Neurosurg., 2, 504-508 (1989).
C. Speciale and R. Schwarcz: Uptake of kynurenine into rat brain slices. J. Neurochem., 54, 156-163 (1990).
E. Westerberg, K. Magnusson, T. Wieloch, U. Ungerstedt, C. Speciale and R. Schwarcz: Extracellular levels of quinolinic acid are moderately increased in rat neostriatum following severe insulin-induced hypoglycemia. Acta Physiol. Scand., 138, 417-422 (1990).
F. Du, E. Okuno, W.O. Whetsell Jr., C. Köhler and R. Schwarcz: Distribution of quinolinic acid phosphoribosyltransferase in the human hippocampal formation and parahippocampal gyrus. J. Comp. Neurol., 295, 71-82 (1990).
H. Baran and R. Schwarcz: Presence of 3-hydroxyanthranilic acid in rat tissues and evidence for its production from anthranilic acid in the brain. J. Neurochem., 55, 738-744 (1990).
C. Speciale, H.-Q. Wu, J.B.P. Gramsbergen, W.A. Turski, U. Ungerstedt and R. Schwarcz: Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: effect of aminooxyacetic acid. Neurosci. Lett., 116, 198-203 (1990).
A. Vezzani, J.B.P. Gramsbergen, P. Versari, M.A. Stasi, F. Procaccio and R. Schwarcz: Kynurenic acid synthesis by human glioma. J. Neurol. Sci., 99, 51-57 (1990).
E. Okuno, F. Du, T. Ishikawa, M. Tsujimoto, M. Nakamura, R. Schwarcz and R. Kido: Purification and characterization of kynurenine-pyruvate aminotransferase from rat kidney and brain. Brain Res., 534, 37-44 (1990).
S.J. Kish, F. Du, D.A. Parks, Y. Robitaille, M.J. Ball, L. Schut, O. Hornykiewicz and R. Schwarcz: Quinolinic acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy. Ann. Neurol., 29, 100-104 (1991).
E. Okuno, M. Nakamura and R. Schwarcz: Two kynurenine aminotransferases in human brain. Brain Res., 542, 307-312 (1991).
F. Du, E. Okuno, W.O. Whetsell, Jr., C. Köhler and R. Schwarcz: Immunohistochemical localization of quinolinic acid phosphoribosyltransferase in the human neostriatum. Neuroscience, 42, 397-406 (1991).
T. Andersson, M. Schultzberg, R. Schwarcz, A. Löve, C. Wickman and K. Kristensson: NMDA-receptor antagonist prevents measles virus induced neurodegeneration. Eur. J. Neurosci., 3, 66-71 (1991).
S. Fukui, R. Schwarcz, S.I. Rapoport, Y. Takada and Q.R. Smith: Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J. Neurochem., 56, 2007-2017 (1991).
H.-Q. Wu, W.A. Turski, U. Ungerstedt and R. Schwarcz: Systemic kainic acid administration in rats: effects on kynurenic acid production in vitro and in vivo. Exp. Neurol., 113, 47-52 (1991).
E. Okuno, W. Schmidt, D.A. Parks, M. Nakamura and R. Schwarcz: Measurement of rat brain kynurenine aminotransferase at physiological kynurenine concentrations. J. Neurochem., 57, 533-540 (1991).
J.L. Walsh, W.P. Todd, B.K. Carpenter and R. Schwarcz: 4-Halo-3-hydroxyanthranilic acids: potent competitive inhibitors of 3-hydroxyanthranilic acid oxygenase in vitro. Biochem. Pharmacol., 42, 985-990 (1991).
O.G. McMaster, F. Du, E.D. French and R. Schwarcz: Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. Exp. Neurol., 113, 367-374 (1991).
M.R. Poston, M.S. Bailey, R. Schwarcz and M.T. Shipley: Differential complementary localization of metabolic enzymes for quinolinic acid in olfactory bulb astrocytes. J. Comp. Neurol., 311, 367-374 (1991).
H.-Q. Wu, U. Ungerstedt and R. Schwarcz: Regulation of kynurenic acid synthesis studied by microdialysis in the dorsal hippocampus of unanesthetized rats. Eur. J. Pharmacol., 213, 375-380 (1992).
F. Du, W. Schmidt, E. Okuno, R. Kido, C. Köhler and R. Schwarcz: Localization of kynurenine aminotransferase immunoreactivity in the rat hippocampus. J. Comp. Neurol., 321, 477-487 (1992).
J.B.P. Gramsbergen, W. Schmidt, W.A. Turski and R. Schwarcz: Age-related changes in kynurenic acid production in rat brain. Brain Res., 588, 1-5 (1992).
R.C. Roberts, F. Du, K. McCarthy, E. Okuno and R. Schwarcz: Immunocytochemical localization of kynurenine aminotransferase in the rat striatum. A light and electron microscopic study. J. Comp. Neurol., 326, 82-90 (1992).
F. Du and R. Schwarcz: Aminooxyacetic acid causes selective neuronal loss in layer III of the rat medial entorhinal cortex. Neurosci. Lett., 147, 185-188 (1992).
H.-Q. Wu, H. Baran, U. Ungerstedt and R. Schwarcz: Kynurenic acid in the quinolinate-lesioned rat hippocampus: studies in vitro and in vivo. Eur. J. Neurosci., 4, 1264-1270 (1992).
C. Speciale and R. Schwarcz: On the production and disposition of quinolinic acid in rat brain and liver slices. J. Neurochem., 60, 212-218 (1993).
R. Schwarcz: Metabolism and function of brain kynurenines. Biochem. Soc. Trans., 21, 77-82 (1993).
D.A. Jauch, V.H. Sethy, B.G. Weick, T.N. Chase and R. Schwarcz: Intravenous administration of L-kynurenine to rhesus monkeys: effect on quinolinate and kynurenate levels in serum and cerebrospinal fluid. Neuropharmacology, 32, 467-472 (1993).
W. Schmidt, P. Guidetti, E. Okuno and R. Schwarcz: Characterization of human brain kynurenine aminotransferases using [3H]kynurenine as a substrate. Neuroscience, 55, 177-184 (1993).
F. Du, J. Williamson, E. Bertram, E. Lothman, E. Okuno and R. Schwarcz: Kynurenine pathway enzymes in a rat model of chronic epilepsy: immunohistochemical study of activated glial cells. Neuroscience, 55, 975-989 (1993).
H. Baran and R. Schwarcz: Regional differences in the ontogenetic pattern of kynurenine aminotransferase in the rat brain. Dev. Brain Res., 74, 283-286 (1993).
T. Andersson, R. Schwarcz, A. Löve and K. Kristensson: Measles virus-induced hippocampal neurodegeneration in the mouse: a novel, subacute model for testing neuroprotective agents. Neurosci. Lett., 154, 109-112 (1993).
F. Du, W.O. Whetsell, Jr., B. Abou-Khalil, B. Blumenkopf, E.W. Lothman and R. Schwarcz: Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Epilepsy Res., 16, 223-233 (1993).
O.G. McMaster, H. Baran, H.-Q. Wu, F. Du, E. French and R. Schwarcz: Gamma-acetylenic GABA produces axon-sparing neurodegeneration after focal injection into the rat hippocampus. Exp. Neurol., 124, 184-191 (1993).
H. Baran, E. Okuno, R. Kido and R. Schwarcz: Purification and characterization of kynurenine aminotransferase I from human brain. J. Neurochem., 62, 730-738 (1994).
J.L. Walsh, H.-Q. Wu, U. Ungerstedt and R. Schwarcz: 4-Chloro-3-hydroxyanthranilate inhibits quinolinate production in the rat hippocampus in vivo. Brain Res. Bull., 33, 513-516 (1994).
C.L. Eastman, E. Urbanska, A. Löve, K. Kristensson and R. Schwarcz: Increased brain quinolinic acid production in mice infected with a hamster neurotropic measles virus. Exp. Neurol., 125, 119-124 (1994).
H.-Q. Wu, R. Schwarcz and P.D. Shepard: Excitatory amino acid-induced excitation of dopamine-containing neurons in the rat substantia nigra: modulation by kynurenic acid. Synapse, 16, 219-230 (1994).
F.G. Salituro, R.C. Tomlinson, B.M. Baron, M.G. Palfreyman, I.A. McDonald, W. Schmidt, H.-Q. Wu, P. Guidetti and R. Schwarcz: Enzyme activated antagonists of the strychnine-insensitive glycine/NMDA receptor. J. Med. Chem., 37, 334-336 (1994).
C.L. Eastman, E.M. Urbanska, A.G. Chapman and R. Schwarcz: Differential expression of the astrocytic enzymes 3-hydroxyanthranilic acid oxygenase, kynurenine aminotransferase and glutamine synthetase in seizure-prone and non-epileptic mice. Epil. Res., 18, 185-194 (1994).
P. Malherbe, C. Köhler, M. Da Prada, G. Lang, V. Kiefer, R. Schwarcz, H.-W. Lahm and A.M. Cesura: Molecular cloning and functional expression of human 3-hydroxyanthranilic acid dioxygenase. J. Biol. Chem., 269, 13792-13797 (1994).
R.C. Roberts, K.E. McCarthy, F. Du, E. Okuno and R. Schwarcz: Immunocytochemical localization of the quinolinic acid synthesizing enzyme, 3-hydroxyanthranilic acid oxygenase, in the rat substantia nigra. Brain Res., 650, 229-238 (1994).
P. Guidetti, J.L. Walsh and R. Schwarcz: A fluorimetric assay for the determination of anthranilic acid in biological materials. Anal. Biochem., 220, 181-184 (1994).
M. Mosca, L. Cozzi, J. Breton, C. Speciale, E. Okuno, R. Schwarcz and L. Benatti: Molecular cloning of rat kynurenine aminotransferase: identity with glutamine transaminase K. FEBS Lett., 353, 21-24 (1994).
S. Ferré, R. Schwarcz, X.M. Li, P. Snaprud, S.O. Ögren and K. Fuxe: Chronic haloperidol treatment leads to an increase in the intramembrane interaction between adenosine A2 and dopamine D2 receptors in the neostriatum. Psychopharmacology, 116, 279-284 (1994).
R.C. Roberts, K.E. McCarthy, F. Du, O.P. Ottersen, E. Okuno and R. Schwarcz: 3-Hydroxyanthranilic acid oxygenase-containing astrocytic processes surround glutamate-containing axon terminals in the rat striatum. J. Neurosci., 15, 1150-1161 (1995).
D. Jauch, E. Urbanska, P. Guidetti, E.D. Bird, J-P.G. Vonsattel, W.O. Whetsell and R. Schwarcz: Dysfunction of brain kynurenic acid metabolism in Huntington's disease: focus on kynurenine aminotransferases. J. Neurol. Sci., 130, 39-47 (1995).
T. Eid, F. Du and R. Schwarcz: Differential neuronal vulnerability to aminooxyacetic acid and quinolinic acid in the rat parahippocampal region. Neuroscience, 68, 645-656 (1995).
H.-Q. Wu, U. Ungerstedt and R. Schwarcz: L-α-Aminoadipic acid as a regulator of kynurenic acid production in the hippocampus: a microdialysis study in freely moving rats. Eur. J. Pharmacol., 281, 55-61 (1995).
P. Guidetti, C.L. Eastman and R. Schwarcz: Metabolism of 5-3H-kynurenine in the rat brain in vivo: evidence for the existence of a functional kynurenine pathway. J. Neurochem., 65, 2621-2632 (1995).
F. Du, T. Eid, E.W. Lothman, C. Köhler and R. Schwarcz: Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. J. Neurosci., 15, 6301-6313 (1995).
H.-Q. Wu, A. Monno, R. Schwarcz and A. Vezzani: Electrical kindling is associated with a lasting increase in the extracellular levels of kynurenic acid in the rat hippocampus. Neurosci. Lett., 198, 91-94 (1995).
H.-Q. Wu and R. Schwarcz: Seizure activity causes elevation of endogenous extracellular kynurenic acid in the rat brain. Brain Res. Bull., 39, 155-162 (1996).
M. Varasi, A. Della Torre, F. Heidempergher, P. Pevarello, C. Speciale, P. Guidetti, D.R. Wells and R. Schwarcz: Derivatives of kynurenine as inhibitors of rat brain kynurenine aminotransferase. Eur. J. Med. Chem., 31, 11-21 (1996).
D. Giulian, J. Yu, X. Li, D. Tom, J. Li, E. Wendt, S.-N. Lin, R. Schwarcz and C. Noonan: Study of receptor-mediated neurotoxins released by HIV-1-infected mononuclear phagocytes found in human brain. J. Neurosci., 16, 3139-3153 (1996).
G. Ceresoli, M.S. Fuller and R. Schwarcz: Excitotoxic lesions of the rat striatum: different responses of kynurenine pathway enzymes during ontogeny. Dev. Brain Res., 92, 61-69 (1996).
T. Eid, B. Jorritsma-Byham, R. Schwarcz and M.P. Witter: Afferents to the seizure-sensitive neurons in layer III of the medial entorhinal area: a tracing study in the rat. Exp. Brain Res., 109, 209-218 (1996).
M.J. Tsai, Y.-F. Chang, R. Schwarcz and N. Brookes: Characterization of L-α-aminoadipic acid transport in cultured rat astrocytes. Brain Res., 741, 166-173 (1996).
C. Speciale, H.-Q. Wu, M. Cini, M. Marconi, M. Varasi and R. Schwarcz: (R,S)-3,4-dichloro-benzoylalanine (FCE 28833A) causes a large and persistent increase in brain kynurenic acid levels in rats. Eur. J. Pharmacol., 315, 263-267 (1996).
M. Hokari, H.-Q. Wu, R. Schwarcz and Q.R. Smith: Facilitated brain uptake of 4-chloro-kynurenine and conversion to 7-chlorokynurenic acid. NeuroReport, 8, 15-18 (1996).
H.-Q. Wu, F.G. Salituro and R. Schwarcz: Enzyme-catalyzed production of the neuroprotective NMDA receptor antagonist 7-chlorokynurenic acid in the rat brain in vivo. Eur. J. Pharmacol., 319, 13-20 (1997).
G. Ceresoli, P. Guidetti and R. Schwarcz: Metabolism of [5-3H]-kynurenine in the developing rat brain in vivo: effect of intrastriatal ibotenate injections. Dev. Brain Res., 100, 73-81 (1997).
J.B.P. Gramsbergen, P.S. Hodgkins, A. Rassoulpour, W.A. Turski, P. Guidetti and R. Schwarcz: Brain-specific modulation of kynurenic acid synthesis in the rat. J. Neurochem., 69, 290-298 (1997).
P. Guidetti, E. Okuno and R. Schwarcz: Characterization of rat brain kynurenine amino-transferases I and II. J. Neurosci. Res., 50, 457-465 (1997).
S.O. Ögren, S. Ferré, R. Schwarcz and K. Fuxe: Prolonged treatment with haloperidol and clozapine in the rat: differential effects on spontaneous and theophylline-induced motor activity. Neurosci. Lett. 232, 21-24 (1997).
F. Du, T. Eid and R. Schwarcz: Neuronal damage after the injection of aminooxyacetic acid into the rat entorhinal cortex: a silver impregnation study. Neuroscience, 82, 1165-1178 (1998).
R. Schwarcz, B. Poeggeler, A. Rassoulpour, G. Ceresoli-Borroni and P.S. Hodgkins: Regulation of kynurenic acid levels in the developing rat brain. Amino Acids, 14, 243-249 (1998).
B. Poeggeler, A. Rassoulpour, P. Guidetti, H.-Q. Wu and R. Schwarcz: Dopaminergic control of kynurenate levels and NMDA toxicity in the developing rat striatum. Dev. Neurosci., 20, 146-153 (1998).
P.S. Hodgkins and R. Schwarcz: Interference with cellular energy metabolism reduces kynurenic acid formation in rat brain slices: reversal by lactate and pyruvate. Eur. J. Neurosci., 10, 1986-1994 (1998).
P.S. Hodgkins and R. Schwarcz: Metabolic control of kynurenic acid formation in the rat brain. Dev. Neurosci., 20, 408-416 (1998).
A. Rassoulpour, H.-Q. Wu, B. Poeggeler and R. Schwarcz: Systemic d-amphetamine administration causes a reduction of kynurenic acid levels in rat brain. Brain Res., 802, 111-118 (1998).
H.-Q. Wu and R. Schwarcz: Focal microinjection of γ-acetylenic GABA into the rat entorhinal cortex: behavioral and electroencephalographic abnormalities, and preferential neuron loss in layer III. Exp. Neurol., 153, 203-213 (1998).
H.E. Scharfman, J.H. Goodman, F. Du and R. Schwarcz: Chronic changes in synaptic responses of entorhinal and hippocampal neurons after entorhinal cortical cell loss produced by intracortical amino-oxyacetic acid (AOAA) injection: an in vitro and in vivo study in the rat. J. Neurophysiol., 80, 3031-3046 (1998).
P.S. Hodgkins, H.-Q. Wu, H.R. Zielke and R. Schwarcz: 2-Oxoacids regulate kynurenic acid production in the rat brain: studies in vitro and in vivo. J. Neurochem., 72, 643-651 (1999).
B. Poeggeler, M.A. Pappolla, R. Hardeland, A. Rassoulpour, P.S. Hodgkins, P. Guidetti, and R. Schwarcz: Indole-3-propionic acid: a potent hydroxyl radical scavenger in rat brain. Brain Res., 815, 382-388 (1999).
G. Ceresoli-Borroni, P. Guidetti and R. Schwarcz: Acute and chronic changes in kynurenate formation following an intrastriatal quinolinate injection in rats. J. Neural Transm., 106, 229-242 (1999).
T. Eid, R. Schwarcz and O.P. Ottersen: Ultrastructure and immunocytochemical distribution of GABA in layer III of the rat medial entorhinal cortex following aminooxyacetic acid-induced seizures. Exp. Brain Res., 125, 463-475 (1999).
M. Linderberg, S. Hellberg, S. Björk, B. Gotthammar, T. Högberg, K. Persson, R. Schwarcz, J. Luthman and R. Johansson: Synthesis and GSAR of substituted 3-hydroxyanthranilic acid derivatives as inhibitors of 3-hydroxyanthranilic acid dioxygenase (3-HAO). Eur. J. Med. Chem., 34, 729-744 (1999).
P. Guidetti and R. Schwarcz: 3-Hydroxykynurenine potentiates quinolinate but not NMDA toxicity in the rat striatum. Eur. J. Neurosci., 11, 3857-3863 (1999).
H.E. Scharfman, P.S. Hodgkins, S.-C. Lee and R. Schwarcz: Quantitative differences in the effects of de novo produced and exogenous kynurenic acid in rat brain slices. Neurosci. Lett., 274, 111-114 (1999).
B. Fornstedt-Wallin, J. Lundström, G. Fredriksson, R. Schwarcz and J. Luthman: 3-Hydroxyanthranilic acid accumulates following administration of the 3-hydroxyanthranilic acid 3,4-dioxygenase inhibitor, 4,6-di-bromo-3-hydroxyanthranilic acid (NCR-631) in rats. Eur. J. Pharmacol., 386, 15-24 (1999).
J.T. Coyle and R. Schwarcz: Mind glue: Implications of glial cell biology for psychiatry. Arch. Gen. Psychiat., 57, 90-93 (2000).
H.-Q. Wu, S.-C. Lee and R. Schwarcz: Systemic administration of 4-chlorokynurenine prevents quinolinate neurotoxicity in the rat hippocampus. Eur. J. Pharmacol., 390, 267-274 (2000).
P. Guidetti, P. H. Reddy, D.A. Tagle and R. Schwarcz: Early kynurenergic impairment in Huntington’s disease and in a transgenic animal model. Neurosci. Lett., 283, 233-235 (2000).
H.-Q. Wu, P. Guidetti, J.H. Goodman, M. Varasi, G. Ceresoli-Borroni, C. Speciale, H.E. Scharfman and R. Schwarcz: Kynurenergic manipulations influence excitatory amino acid receptor function and excitotoxic vulnerability in the rat hippocampus in vivo. Neuroscience, 97, 243-251 (2000).
P. Guidetti, H.-Q. Wu and R. Schwarcz: In situ produced 7-chlorokynurenate provides protection against quinolinate- and malonate-induced neurotoxicity. Exp. Neurol., 163, 123-130 (2000).
H.E. Scharfman, J.H. Goodman and R. Schwarcz: Electrophysiological effects of exogenous and endogenous kynurenic acid in the rat brain: studies in vivo and in vitro. Amino Acids, 19, 283-297 (2000).
G. Ceresoli-Borroni and R. Schwarcz: Perinatal kynurenine pathway metabolism in the normal and asphyctic rat brain. Amino Acids, 19, 311-323 (2000).
G. Battaglia, A. Rassoulpour, H.-Q. Wu, P.S. Hodgkins, C. Kiss, F. Nicoletti and R. Schwarcz: Some metabotropic glutamate receptor ligands reduce kynurenate synthesis in rats by intracellular inhibition of kynurenine aminotransferase II. J. Neurochem., 75, 2051-2060 (2000).
R. Schwarcz: Glutamate 2000: Old dog, new tricks. J. Pharmacol. Exp. Therap., 296, 659-662 (2001).
P. Guidetti, V. Charles, H. Reddy, W.O. Whetsell, R. Schwarcz and D. Tagle: Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp. Neurol., 169, 340-350 (2001).
S.-C. Lee and R. Schwarcz: Excitotoxic injury stimulates pro-drug-induced 7-chlorokynurenate formation in the rat striatum in vivo. Neurosci. Lett., 304, 185-188 (2001).
G. Ceresoli-Borroni and R. Schwarcz: Neonatal asphyxia in rats: acute effects on cerebral kynurenine metabolism. Pediatr. Res., 50, 231-235 (2001).
T. Eid, F. Du and R. Schwarcz: Ibotenate injections into the pre- and parasubiculum provide partial protection against kainate-induced epileptic damage in layer III of rat entorhinal cortex. Epilepsia, 42, 817-824 (2001).
C. Hilmas, E.F.R. Pereira, M. Alkondon, A. Rassoulpour, R. Schwarcz and E.X. Albuquerque: The brain metabolite kynurenic acid inhibits a7 nicotinic receptor activity and increases non-a7 nicotinic receptor expression: physiopathological implications. J. Neurosci., 21, 7463-7473 (2001).
R. Schwarcz, A. Rassoulpour, H.-Q. Wu, D. Medoff, C.A. Tamminga and R.C. Roberts: Increased cortical kynurenate content in schizophrenia. Biol. Psychiatry, 50, 521-530 (2001).
E. Lehrmann, A. Molinari, C. Speciale and R. Schwarcz: Immunohistochemical visualization of newly formed quinolinate in the normal and excitotoxically lesioned rat striatum. Exp. Brain. Res., 141, 389-397 (2001).
M.J. Denslow, T. Eid, F. Du, R. Schwarcz, E.W. Lothman and O. Steward: Disruption of inhibition in area CA1 of the hippocampus in a rat model of temporal lobe epilepsy. J. Neurophysiol., 86, 2231-2245 (2001).
H.-Q. Wu, A. Rassoulpour and R. Schwarcz: Effect of systemic L-dopa administration on extracellular kynurenate levels in the rat striatum. J. Neural Transm., 109, 239-249 (2002).
R. Schwarcz and R. Pellicciari: Manipulation of brain kynurenines: glial targets, neuronal effects and clinical opportunities. J. Pharmacol. Exp. Therap., 303, 1-10 (2002).
R. Schwarcz and M.P. Witter: Memory impairment in temporal lobe epilepsy: the role of entorhinal lesions. Epil. Res., 50, 161-177 (2002).
H.-Q. Wu, S.-C. Lee, H.E. Scharfman and R. Schwarcz: L-4-Chlorokynurenine attenuates kainate-induced seizures and lesions in the rat. Exp. Neurol., 177, 222-232 (2002).
C. Kiss, G. Ceresoli-Borroni, P. Guidetti, C.L. Zielke, H.R. Zielke and R. Schwarcz: Kynurenate production by cultured human astrocytes. J. Neural Transm., 110, 1-14 (2003).
P.D. Shepard, B. Joy, L. Clerkin and R. Schwarcz: Micromolar brain levels of kynurenic acid are associated with a disruption of auditory sensory gating in the rat. Neuropsychopharmacology, 28, 1454-1462 (2003).
P. Guidetti and R. Schwarcz: Determination of a-aminoadipic acid in brain, peripheral tissues and body fluids using GC/MS with negative chemical ionization. Brain Res. Mol. Brain Res., 118, 132-139 (2003).
R. Schwarcz: The kynurenine pathway of tryptophan degradation as a drug target. Curr. Opin. Pharmacol., 4, 12-17 (2004).
C. Kiss, P.D. Shepard, F. Bari and R. Schwarcz: Cortical spreading depression augments kynurenate levels and reduces malonate toxicity in the rat cortex. Brain Res., 1002, 129-135 (2004).
M. Alkondon, E.F.R. Pereira, P.Yu, E.Z. Arruda, L.E.F. Almeida, P. Guidetti, W.P. Fawcett, M. T. Sapko, W.R. Randall, R. Schwarcz, D.A. Tagle and E.X. Albuquerque: Targeted deletion of the kynurenine aminotransferase II gene reveals a critical role of endogenous kynurenic acid in the regulation of synaptic transmission via α7 nicotinic receptors in the hippocampus. J. Neurosci., 24, 4635-4648 (2004).
H.-Q. Wu, K. Fuxe and R. Schwarcz: Neuronal A1 receptors mediate increase in extracellular kynurenic acid after local intrastriatal adenosine infusion. J. Neurochem., 90, 621-628 (2004).
P. Yu, N.A. Di Prospero, M.T. Sapko, T. Cai, A Chen, M. Melendez-Ferro, F. Du, W.O. Whetsell Jr., P. Guidetti, R. Schwarcz and D.A. Tagle: Biochemical and phenotypic abnormalities in kynurenine aminotransferase II-deficient mice. Mol. Cell. Biol., 24, 6919-6930 (2004).
P. Guidetti, R.E. Luthi-Carter, S.J. Augood and R. Schwarcz: Neostriatal and cortical quinolinate levels are increased in early grade Huntington’s Disease. Neurobiol. Dis., 17, 455-461 (2004).
A. Rassoulpour, H.-Q. Wu, E.X. Albuquerque and R. Schwarcz: Prolonged nicotine administration results in bi-phasic, brain-specific changes in kynurenate levels in the rat. Neuropsychopharmacology, 30, 697-704 (2005).
A. Rassoulpour, H.-Q. Wu, S. Ferré and R. Schwarcz: Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum. J. Neurochem., 93, 762-765 (2005).
P. Samadi, L. Gregoire, A. Rassoulpour, P. Guidetti, E. Izzo, R. Schwarcz and P. Bédard: Effect of kynurenine 3-hydroxylase inhibition on the dyskinetic and anti-parkinsonian response to L-Dopa in parkinsonian monkeys. Movement Dis., 20, 792-802 (2005).
H.-Q. Wu, A. Rassoulpour, J. H. Goodman, H.E. Scharfman, E. H. Bertram and R. Schwarcz: Kynurenate and 7-chlorokynurenate formation in chronically epileptic rats. Epilepsia, 46, 1010-1016 (2005).
D.X. Zhang, J.M. Williamson, H.-Q. Wu, R. Schwarcz and E.H. Bertram: In situ produced 7- chlorokynurenate has different effects on evoked responses in rats with limbic epilepsy in comparison to naive controls. Epilepsia, 46, 1708-1715 (2005).
M.T. Sapko, P. Guidetti, P. Yu, D.A. Tagle, R. Pellicciari and R. Schwarcz: Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: implications for Huntington’s disease. Exp. Neurol., 197, 31-40 (2006).
F. Bari, K. Nagy, P. Guidetti, R. Schwarcz, D.W. Busija and F. Domoki: Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs. Brain Res., 1069, 39-46 (2006).
G. Ceresoli-Borroni, A. Rassoulpour, H.-Q. Wu, P. Guidetti and R. Schwarcz: Chronic neuroleptic treatment reduces endogenous kynurenic acid levels in rat brain. J. Neural Transm., 113, 1355-1365 (2006).
R. Pellicciari, R. Rizzo, G. Costantino, M. Marinozzi, L. Amori, P. Guidetti, H.-Q. Wu and R. Schwarcz: Modulators of the kynurenine pathway of tryptophan metabolism. Synthesis and preliminary biological evaluation of (S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor. ChemMedChem, 1, 528-531 (2006).
P. Guidetti, G.P. Bates, R.K. Graham, M.R. Hayden, B.R. Leavitt, M.E. MacDonald, E.J. Slow, V.C. Wheeler, B. Woodman and R. Schwarcz: Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol. Dis., 23, 190-197 (2006).
M.L. Belladonna, U. Grohmann, P. Guidetti, C. Volpi, R. Bianchi, M.C. Fioretti, R. Schwarcz, F. Fallarino and P. Puccetti: Kynurenine pathway enzymes in dendritic cells initiate tolerogenesis in the absence of functional IDO. J. Immunol., 177, 130-137 (2006).
P. Guidetti, G.E. Hoffman, M. Melendez-Ferro, E.X. Albuquerque and R. Schwarcz: Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia, 55, 78-92 (2007).
H.-Q. Wu, A. Rassoulpour and R. Schwarcz: Kynurenic acid leads, dopamine follows: a new case of volume transmission in the brain? J. Neural Transm., 114, 33-41 (2007).
G. Ceresoli-Borroni, P. Guidetti, L. Amori, R. Pellicciari and R. Schwarcz: Perinatal kynurenine 3-hydroxylase inhibition in rodents: pathophysiological implications. J. Neurosci. Res., 85, 845-854 (2007).
M. Alkondon, E.F.R. Pereira, M.C. Potter, F.C. Kauffman, R. Schwarcz and E.X. Albuquerque: Strain-specific nicotinic modulation of glutamatergic transmission in the CA1 field of the rat hippocampus: August Copenhagen Irish versus Sprague-Dawley. J. Neurophysiol., 97, 1163-1170 (2007).
P. Guidetti, L. Amori, M.T. Sapko, E. Okuno and R. Schwarcz: Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J. Neurochem., 102, 103-111 (2007).
R. Schwarcz and C.A. Hunter: Toxoplasma gondii and schizophrenia: linkage through astrocyte-derived kynurenic acid? Schiz. Bull., 33, 652-653 (2007).
C. Lopes, E.F.R. Pereira, H.-Q. Wu, P. Purushottamachar, V. Njar, R. Schwarcz and E.X. Albuquerque: Competitive antagonism between the nicotinic allosteric potentiating ligand galantamine and kynurenic acid at α7* nicotinic receptors. J. Pharmacol. Exp. Therap., 322, 48-58 (2007).
B. Poeggeler, A. Rassoulpour, H.-Q. Wu, P. Guidetti, R.C. Roberts and R. Schwarcz: Dopamine receptor activation reveals a novel, kynurenate-sensitive component of striatal NMDA neurotoxicity. Neuroscience, 148, 188-197 (2007).
L. Grégoire, A. Rassoulpour, P. Guidetti, P. Samadi, P.J. Bédard, E. Izzo, R. Schwarcz and T. Di Paolo: Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys. Behav. Brain Res., 186, 161-167 (2008).
V.H. Brun, S. Leutgeb, H.-Q. Wu, R. Schwarcz, M.P. Witter, E.I. Moser and M.-B. Moser: Impaired spatial representation in CA1 after lesion of direct input from entorhinal cortex. Neuron, 57, 290-302 (2008).
R. Schwarcz: Early glial dysfunction in epilepsy. Epilepsia, 49, Suppl. 2, 1-2 (2008).
E. Lehrmann, P. Guidetti, A. Löve, J. Williamson, E.H. Bertram and R. Schwarcz: Glial activation precedes seizures and hippocampal neurodegeneration in measles virus-infected mice. Epilepsia, 49, Suppl. 2, 13-23 (2008).
F. Giorgini, T. Möller, W. Kwan, D. Zwilling, J.L. Wacker, S. Hong, L.-C.L. Tsai, C.S. Cheah, R. Schwarcz, P. Guidetti and P.J. Muchowski: Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J. Biol. Chem., 283, 7390-7400 (2008).
R. Pellicciari, F. Venturoni, D. Bellocchi, A. Carotti, M.Marinozzi, A. Macchiarulo, L. Amori and R. Schwarcz: Sequence variants in kynurenine aminotransferase II (KAT II) orthologs determine different potencies of the inhibitor S-ESBA. ChemMedChem, 3, 1199-1202 (2008).
F. Rossi, R. Schwarcz and M. Rizzi: Curiosity to kill the KAT (kynurenine aminotransferase): structural insights into brain kynurenic acid synthesis. Curr. Opin. Struct. Biol., 18, 748-755 (2008).
L. Amori, H.-Q. Wu, M. Marinozzi, R. Pellicciari, P. Guidetti and R. Schwarcz: Specific inhibition of kynurenate synthesis enhances extracellular dopamine levels in the rodent striatum. Neuroscience, 159, 196-203 (2009).
A. Zmarowski, H.-Q. Wu, J.M. Brooks, M.C. Potter, R. Pellicciari, R. Schwarcz and J.P. Bruno: Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release. Eur. J. Neurosci., 29, 529-538 (2009).
L. Amori, P. Guidetti, R. Pellicciari, Y. Kajii and R. Schwarcz: On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J. Neurochem., 109, 316-325 (2009).
H.-Q. Wu, E.F.R. Pereira, J.P. Bruno, R. Pellicciari, E.X. Albuquerque and R. Schwarcz: The astrocyte-derived α7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J. Molec. Neurosci., 40, 204-210 (2010).
R. Schwarcz, P. Guidetti, K.V. Sathyasaikumar and P.J. Muchowski: Of mice, rats and men: re-visiting the quinolinic acid hypothesis of Huntington’s Disease. Progr. Neurobiol., 90, 230-245 (2010).
I. Wonodi and R. Schwarcz: Cortical kynurenine pathway metabolism: a novel target for cognitive enhancement in schizophrenia. Schiz. Bull., 36, 211-218 (2010).
K.V. Sathyasaikumar, E.K. Stachowski, L. Amori, P. Guidetti, P.J. Muchowski and R. Schwarcz: Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington’s disease. J. Neurochem., 113, 1416-1425 (2010).
M.C. Potter, G.I. Elmer, R. Bergeron, E.X. Albuquerque, P. Guidetti, H.-Q. Wu and R. Schwarcz: Reduction of endogenous kynurenate formation enhances extracellular glutamate, hippocampal plasticity and cognitive behavior. Neuropsychopharmacology, 35, 1734-1742 (2010).
Å. Konradsson-Geuken, H.-Q. Wu, C.R. Gash, K.S. Alexander, R. Pellicciari, R. Schwarcz and J.P. Bruno: Changes in cortical kynurenic acid bi-directionally modulate prefrontal glutamate levels as assessed by microdialysis and rapid electrochemistry. Neuroscience, 169, 1848-1859 (2010).
F. Rossi, C. Valentina, S. Garavaglia, K.V. Sathyasaikumar, R. Schwarcz, S.-I. Kojima, K. Okuwaki, S.-I. Ono, Y. Kajii and M. Rizzi: Crystal structure-based selective targeting of the PLP-dependent enzyme kynurenine aminotransferase II for cognitive enhancement. J. Med. Chem., 53, 5684-5689 (2010).
M.A. Thevandavakkam, R. Schwarcz, P.J. Muchowski and F. Giorgini: Targeting kynurenine 3- monooxygenase (KMO): implications for therapy in Huntington's disease. Curr. Drug Targ., 9, 791-800 (2010).
K.V. Sathyasaikumar, E.K. Stachowski, I. Wonodi, R.C. Roberts, A. Rassoulpour, R.P. McMahon and R. Schwarcz: Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schiz. Bull., 37, 1147-1156 (2011).
R.W. Buchanan and R. Schwarcz: α7 Nicotinic receptor agonists as cognitive remedies: is less (or less often) more? Biol. Psychiat., 69, 5-6 (2011).
M. Alkondon, E.F.R. Pereira, H.M. Eisenberg, Y. Kajii, R. Schwarcz and E.X. Albuquerque: Age dependency of inhibition of α7 nicotinic receptors and tonically active NMDA receptors by endogenously produced kynurenic acid in the brain. J. Pharmacol. Exp. Therap., 337, 572-582 (2011).
S. Campesan, E.W. Green, C. Breda1, K.V. Sathyasaikumar, P.J. Muchowski, R. Schwarcz, C.P. Kyriacou and F. Giorgini: The kynurenine pathway modulates neurodegeneration in a Drosophila model of Huntington’s disease. Curr. Biol., 21, 961-966 (2011).
D. Zwilling, S.-Y. Huang, K.V. Sathyasaikumar, F.M. Notarangelo, P. Guidetti, H.-Q. Wu, J. Lee, J. Truong, Y. Andrews-Zwilling, E.W. Hsieh, J.Y. Louie, T. Wu, K. Scearce-Levie, C. Patrick, A. Adame, F. Giorgini, S. Moussaoui, G. Laue, A. Rassoulpour, G. Flik, Y. Huang, J.M. Muchowski, E. Masliah, R. Schwarcz and P.J. Muchowski: Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell, 145, 863-874 (2011).
I. Wonodi, O.C. Stine, K.V. Sathyasaikumar, R.C. Roberts, B.D. Mitchell, L.E. Hong, Y. Kajii, G.K. Thaker and R. Schwarcz: Downregulated kynurenine 3-monooxygenase gene expression and enzyme activity in schizophrenia and genetic association with schizophrenia endophenotypes. Arch. Gen. Psychiat., 68, 665-674 (2011).
A. Pocivavsek, H.-Q. Wu, M.C. Potter, G.I. Elmer, R. Pellicciari and R. Schwarcz: Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology, 36, 2357-2367 (2011).
E. Stachowski and R. Schwarcz: Regulation of quinolinic acid neosynthesis in mouse, rat and human brain by iron and iron chelation in vitro. J. Neural Transm., 119, 123-131 (2012).
F.M. Notarangelo, H.-Q. Wu, A. Macherone, D.R. Graham and R. Schwarcz: GC/MS/MS detection of extracellular kynurenine and related metabolites in normal and lesioned rat brain. Anal. Biochem., 421, 573-581 (2012).
K.S. Alexander, H.-Q. Wu, R. Schwarcz and J.P. Bruno: Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. Psychopharmacology, 220, 627-637 (2012).
V. Pérez-De La Cruz, L. Amori, K.V. Sathyasaikumar, X.-D. Wang, F.M. Notarangelo, H.-Q. Wu and R. Schwarcz: Enzymatic transamination of D-kynurenine generates kynurenic acid in rat and human brain. J. Neurochem., 120, 1026-1035 (2012).
A. Pocivavsek, H.-Q. Wu, G.I. Elmer, J.P. Bruno and R. Schwarcz: Pre- and postnatal exposure to kynurenine causes cognitive deficits in adulthood. Eur. J. Neurosci., 35, 1605-1612 (2012).
X.-D. Wang, F.M. Notarangelo, J.-Z. Wang and R. Schwarcz: Kynurenic acid and 3-hydroxykynurenine production from D-kynurenine in mice. Brain Res., 1455, 1-9 (2012).
R. Schwarcz, J.P. Bruno, P.J. Muchowski and H.-Q. Wu: Kynurenines in the mammalian brain: when physiology meets pathology. Nature Rev. Neurosci., 13, 465-477 (2012).
E.W. Green, S. Campesan, C. Breda, K.V. Sathyasaikumar, P.J. Muchowski, R. Schwarcz, C.P. Kyriacou and F. Giorgini: Drosophila eye color mutants as therapeutic tools for Huntington's disease. Fly, 6, 117-120 (2012).
K.S. Alexander, A. Pocivavsek, H.-Q. Wu, M.L. Pershing, R. Schwarcz and J.P. Bruno: Early developmental elevations of brain kynurenic acid impair cognitive flexibility in adults: reversal with galantamine. Neuroscience, 238, 19-28 (2013).
S. Beggiato, T. Antonelli, M.C. Tomasini, S. Tanganelli, K. Fuxe, R. Schwarcz and L. Ferraro: Kynurenic acid, by targeting α7 nicotinic acetylcholine receptors, modulates extracellular GABA levels in the rat striatum in vivo. Eur. J. Neurosci., 37, 1470-1477 (2013).
E.X. Albuquerque and R. Schwarcz: Kynurenic acid as an antagonist of α7 nicotinic receptors in the brain: facts and challenges. Biochem. Pharmacol., 85, 1027-1032 (2013).
Z. Justinova, P. Mascia, H.-Q. Wu, M.E. Secci, G.H. Redhi, L.V. Panlilio, M. Scherma, C. Barnes, A. Parashos, T. Zara, W. Fratta, M. Solinas, M. Pistis, J. Bergman, B.D. Kangas, S. Ferré, G. Tanda, R. Schwarcz and S.R. Goldberg: Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nature Neurosci., 16, 1652-1661 (2013).
F. Giorgini, S.-Y. Huang, K.V. Sathyasaikumar, F.M. Notarangelo, M.A.R. Thomas, M. Tararina, H.-Q. Wu, R. Schwarcz and P.J. Muchowski: Targeted deletion of kynurenine 3-monooxygenase (KMO) in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain. J. Biol. Chem., 288, 36554-36566 (2013).
X.-D. Wang, K.J. Horning, F.M. Notarangelo and R. Schwarcz: A method for the determination of D-kynurenine in biological tissues. Anal. Bioanal. Chem., 405, 9747-9754 (2013).
G.P. Vallerini, L. Amori, C. Beato, M. Tararina, X.-D. Wang, R. Schwarcz and G. Costantino: 2-Aminonicotinic acid 1-oxides are chemically stable inhibitors of quinolinic acid synthesis in the mammalian brain: a step towards new anti-excitotoxic agents. J. Med. Chem., 56, 9482-9495 (2013).
F.M. Notarangelo, E.H. Wilson, K.J. Horning, M.A.R. Thomas, T.H. Harris, Q. Fang, C.A. Hunter, R. Schwarcz: Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia. Schiz. Res., 152, 261-267 (2014).
H.-Q. Wu, M. Okuyama, Y. Kajii, A. Pocivavsek, J.P. Bruno and R. Schwarcz: Targeting kynurenine aminotransferase II in psychiatric diseases: promising effects of an orally active enzyme inhibitor. Schiz. Bull., 40, S152-S158 (2014).
A. Pocivavsek, M.A.R. Thomas, G.I. Elmer, J.P. Bruno and R. Schwarcz: Continuous kynurenine administration during the prenatal period, but not during adolescence,causes learning and memory deficits in adult rats. Psychopharmacology, 231, 2799-2809 (2014).
S. Beggiato, S. Tanganelli, K. Fuxe, T. Antonelli, R. Schwarcz and L. Ferraro: Endogenous kynurenic acid regulates extracellular GABA levels in the rat prefrontal cortex. Neuropharmacology, 82, 11-18 (2014).
J. Chiappelli, A. Pocivavsek, K.L. Nugent, F.M. Notarangelo, P. Kochunov, L.M. Rowland, R. Schwarcz and L.E. Hong: Stress-induced increase in kynurenic acid as a potential biomarker for patients with schizophrenia and distress intolerance. JAMA Psychiatry, 71, 761-768 (2014).
M.L. Pershing, D.M. Bortz, A. Pocivavsek, P.J. Fredericks, C.V. Jørgensen, S.A. Vunck, B. Leuner, R. Schwarcz and J.P. Bruno: Elevated levels of kynurenic acid during gestation produce neurochemical, morphological, and cognitive deficits in adulthood: implications for schizophrenia. Neuropharmacology, 90, 33-41 (2015).
J.L. Drewes, K.A. Meulendyke, Z. Liao, K.W. Witwer, L. Gama, C. Ubaida-Mohien, M. Li, F.M. Notarangelo, P.M. Tarwater, R. Schwarcz, D.R. Graham, M.C. Zink: Quinolinic acid/tryptophan ratios predict neurological disease in SIV-infected macaques and remain elevated in the brain under cART. J. Neurovirol., 21, 449-463 (2015).
T. Blanco-Ayala, R. Lugo-Huitrón, L. Carmona-Aparicio, D. Ramírez Ortega, D. González Esquivel, J. Pedraza-Chaverrí, G. Pérez-de la Cruz, C. Ríos, R. Schwarcz and V. Pérez-de la Cruz: Alternative kynurenic acid synthesis routes studied in the rat cerebellum. Front. Cell. Neurosci., 9, Article 178 (2015).
F.M. Notarangelo, X.-D. Wang, K.J. Horning and R. Schwarcz: Role of D-amino acid oxidase in the production of kynurenine pathway metabolites from D-tryptophan in mice. J Neurochem., 136, 804-814 (2016).
S.M. Clark, A. Pocivavsek, J.D. Nicholson, F.M. Notarangelo, P. Langenberg, R.P. McMahon, J.E. Kleinman, T.M. Hyde, J. Stiller, T.T. Postolache, R. Schwarcz and L.H. Tonelli: Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals. J. Psychiat. Neurosci., 41, 150226 (2016).
C. Breda, K.V. Sathyasaikumar, S.S. Idrissi, F.M. Notarangelo, J.G. Estranero, G.G.L. Moore, E.W. Green, C.P. Kyriacou, R. Schwarcz and F. Giorgini: Tryptophan-2,3-dioxygenase (TDO) inhibition ameliorates neurodegeneration by modulation of kynurenine pathway metabolites. Proc. Natl. Acad. Sci. (U.S.A.), 113, 5435-5440 (2016).
P.B. Larkin, K.V. Sathyasaikumar, F.M. Notarangelo, H. Funakoshi, T. Nakamura, R. Schwarcz and P.J. Muchowski: Tryptophan 2,3-dioxygenase and indoleamine 2,3-dioxygenase 1 make separate, tissue-specific contributions to basal and inflammation-induced kynurenine pathway metabolism in mice. Biochim. Biophys. Acta, 1860, 2345-2354 (2016).
M.L. Pershing, D. Phenis, V. Valentini, A. Pocivavsek, D.H. Lindquist, R. Schwarcz and J.P. Bruno: Prenatal kynurenine exposure results in age-dependent changes in NMDA receptor expression and conditioned fear responding. Psychopharmacology, 233, 3725-3735 (2016).
F.M. Notarangelo and R. Schwarcz: Restraint stress during pregnancy rapidly raises kynurenic acid levels in mouse placenta and fetal brain. Dev. Neurosci., 38, 458-468 (2016).
S. Erhardt, A. Pocivavsek, M. Repici, X.-C. Liu, S. Imbeault, D.C. Maddison, M.A.R. Thomas, J.L. Smalley, M.K. Larsson, P.J. Muchowski, F. Giorgini and R. Schwarcz: Adaptive and behavioral changes in kynurenine 3-monooxygenase knockout mice: relevance to psychotic disorders. Biol. Psychiatry, 82, 756-765 (2017).
R. Schwarcz and T.W. Stone: The kynurenine pathway and the brain: challenges, controversies and promises. Neuropharmacology, 112 (Pt B), 237-247 (2017).
D.M. Bortz, H.-Q. Wu, R. Schwarcz and J.P. Bruno: Oral administration of a specific kynurenic acid synthesis (KAT II) inhibitor attenuates evoked glutamate release in rat prefrontal cortex. Neuropharmacology, 121, 69-78 (2017).
M. Secci, A. Auber, L. Panlilio, G. Redhi, E. Thorndike, C. Schindler, R. Schwarcz, S.R. Goldberg and Z. Justinova: Attenuating nicotine reinforcement and relapse by enhancing endogenous brain levels of kynurenic acid in rats and squirrel monkeys. Neuropsychopharmacology, 42, 1619-1629 (2017).
E. Flores-Barrera, D.R. Thomases, D.K. Cass, A. Bhandari, R. Schwarcz, J.P. Bruno and K.Y. Tseng: Preferential disruption of prefrontal GABAergic function by nanomolar concentrations of the α7nACh negative modulator kynurenic acid. J. Neurosci., 37, 7921–7929 (2017).
T.L. Yaksh, R. Schwarcz and H.R. Snodgrass: Characterization of the effects of L-4‑chlorokynurenine on nociception in rodents. J. Pain, 18, 1184-1196 (2017).
K.V. Sathyasaikumar, M. Tararina, H.-Q. Wu, S.A. Neale, F. Weisz, T.E. Salt and R. Schwarcz: Xanthurenic acid formation from 3-hydroxykynurenine in the mammalian brain: neurochemical characterization and physiological effects. Neuroscience, 367, 85-97 (2017).
N. Goeden, F.M. Notarangelo, A. Pocivavsek, S. Beggiato, A. Bonnin and R. Schwarcz: Prenatal dynamics of kynurenine pathway metabolism in mice: focus on kynurenic acid. Dev. Neurosci., 39, 519-528 (2017).
C. Song, S.M. Clark, C.N. Vaughn, J.D. Nicholson, K.J. Murphy, T.-C. M. Mou, R. Schwarcz, G.E. Hoffman and L.H. Tonelli: Quantitative analysis of kynurenine aminotransferase II in the adult rat brain reveals high expression in proliferative zones and corpus callosum. Neuroscience, 369, 1-14 (2018).
B. Hahn, C.H. Reneski, A. Pocivavsek and R. Schwarcz: Prenatal kynurenine treatment in rats causes schizophrenia-like broad monitoring deficits in adulthood. Psychopharmacology, 235, 651-661 (2018).
J. Chiappelli, F.M. Notarangelo, A. Pocivavsek, M.A.R. Thomas, L.M. Rowland, R. Schwarcz and L.E. Hong: Influence of plasma cytokines on kynurenine and kynurenic acid in schizophrenia. Neuropsychopharmacology, 43, 1675-1680 (2018).
F.M. Notarangelo, A. Pocivavsek and R. Schwarcz: Exercise your kynurenines to fight depression. Trends Neurosci., 41, 491-493 (2018).
M. Tufvesson-Alm, L. Schwieler, R. Schwarcz, M Goiny, S. Erhardt and G. Engberg: Importance of kynurenine 3-monooxygenase for spontaneous firing and pharmacological responses of midbrain dopamine neurons: relevance for schizophrenia. Neuropharmacology, 138, 130-139 (2018).
J. Chiappelli, L.M. Rowland, F.M. Notarangelo, S.A. Wijtenburg, M.A.R. Thomas, A. Pocivavsek, A. Jones, K. Wisner, P. Kochunov, R. Schwarcz and L.E. Hong: Salivary kynurenic acid response to psychological stress: inverse relationship to cortical glutamate in schizophrenia. Neuropsychopharmacology, 43, 1706-1711 (2018).
S. Beggiato, F.M. Notarangelo, K.V. Sathyasaikumar, F. Giorgini and R. Schwarcz: Maternal genotype determines kynurenic acid levels in the fetal brain: implications for the pathophysiology of schizophrenia. J. Psychopharmacol., 32, 1223-1232 (2018).
S.M. Clark, F.M. Notarangelo, X. Li, S. Chen, R. Schwarcz and L.H. Tonelli: Maternal immune activation in rats blunts brain cytokine and kynurenine pathway responses to a second immune challenge in early adulthood. Progr. Neuro-Psychopharmacol. & Biol. Psychiatry, 89, 286-294 (2019).
A. Pocivavsek, G.I. Elmer and R. Schwarcz: Inhibition of kynurenine aminotransferase II attenuates hippocampus-dependent memory deficit in adult rats treated prenatally with Hippocampus, 29, 73-77 (2019).
T. Blanco-Ayala, K.V. Sathyasaikumar, J.D. Uys, V. Pérez-de-la-Cruz, L.S. Pidugu and R.T. Blanco-Ayala, K.V. Sathyasaikumar, J.D. Uys, V. Pérez-de-la-Cruz, L.S. Pidugu and
M.E. Secci, P. Mascia, C. Sagheddu, S. Beggiato, M. Melis, A.C. Borelli, M.C. Tomasini, L.V. Panlilio, C.W. Schindler, G. Tanda, S. Ferré, C.W. Bradberry, L. Ferraro, M. Pistis, S.R. Goldberg, R. Schwarcz and Z. Justinova: Astrocytic mechanisms involving kynurenic acid control Δ9-tetrahydrocannabinol-induced increases in glutamate release in brain reward-processing areas. Mol. Neurobiol., 56, 3563-3575 (2019).
F.M. Notarangelo, S. Beggiato and R. Schwarcz: Assessment of prenatal kynurenine metabolism using tissue slices: focus on the neosynthesis of kynurenic acid in mice. Dev. Neurosci., 22, 1-10 (2019).
S. Zhang, M. Sakuma, G.S. Deora, C.W. Levy, A. Klausing, C. Breda, K.D. Read, C.D. Edlin, B.P. Ross, M.W. Muelas, P.J. Day, S. O’Hagan, D.B. Kell, R. Schwarcz, D. Leys, D.J. Heyes, F. Giorgini and N.S. Scrutton: A brain-permeable inhibitor of the neurodegenerative disease target kynurenine 3-monooxygenase prevents accumulation of neurotoxic metabolites. Communic. Biol., 2, 271 (2019).
A.D. Klausing, T. Fukuwatari, D.J. Bucci and R. Schwarcz: Stress-induced impairment in fear discrimination is causally related to increased kynurenic acid formation in the prefrontal cortex. Psychopharmacology, 237, 1931-1941 (2020).
S. Beggiato, A. Ieraci, M.A. Tomasini, R. Schwarcz and L. Ferraro: Prenatal THC exposure raises kynurenic acid levels in the prefrontal cortex of adult rats. Progr. Neuro-Psychopharmacol. & Biol. Psychiatry, 100, 109883 (2020).
D. Phenis, S.A. Vunck, V. Valentini, H. Arias, R. Schwarcz and J.P. Bruno: Activation of alpha7 nicotinic and NMDA receptors is necessary for performance in a working memory task. Psychopharmacology, 237, 1723-1735 (2020).
T. Blanco-Ayala, K.V. Sathyasaikumar, J.D. Uys, V. Pérez-de-la-Cruz, L.S. Pidugu and R. Schwarcz: N-Acetylcysteine inhibits kynurenine aminotransferase II. Neuroscience, 444, 160-168 (2020).
J.T. Coyle and R. Schwarcz: The discovery and characterization of targeted perikaryal-specific brain lesions with excitotoxins. Front. Neurosci., 14, 927 (2020).
T. Blanco-Ayala, D. Ramirez Ortega, P.O. Rodriguez, B. Pineda, G. Pérez de la Cruz, D.G. Esquivel, R. Schwarcz, K.V. Sathyasaikumar, A. Jiménez Anguiano and V. Pérez de la Cruz: Subchronic N-acetylcysteine treatment decreases brain kynurenic acid levels and improves cognitive performance in mice. Antioxidants, 10, 147 (2021).
S. Beggiato, M. Zuccarini, T. Cassano, D. Borroto-Escuela, P. Di Iorio, R. Schwarcz, K. Fuxe and L. Ferraro: Adenosine and kynurenic acid interactions: possible relevance for schizophrenia treatment? Front. Pharmacol., 12, 654426 (2021).
F.N. Notarangelo and R. Schwarcz: A single prenatal lipopolysaccharide injection has acute, but not long-lasting, effects on cerebral kynurenine pathway metabolism in mice. Eur. J. Neurosci., 54, 5968-5981 (2021)
K.V. Sathyasaikumar, V. Pérez de la Cruz, B. Pineda, G.I.V. Cervantes, D. Ramírez Ortega, W. Donley, P.L. Severson, B.L. West, F. Giorgini, J.H. Fox and R. Schwarcz: Cellular localization of kynurenine 3-monooxygenase in the brain: challenging the dogma. Antioxidants, in press.
BOOK CHAPTERS AND INVITED REVIEWS
H.I. Yamamura, R.E. Hruska, R. Schwarcz and J.T. Coyle: Effect of striatal kainic acid lesions on muscarinic cholinergic receptor binding: correlation with Huntington's disease. In: Animal Models in Psychiatry and Neurology (I. Hanin and E. Usdin, eds.), Pergamon, pp. 411-414, 1977.
S.R. Childers, R. Schwarcz, J.T. Coyle and S.H. Snyder: Radioimmunoassay of enkephalins: levels of methionine- and leucine-enkephalin in morphine-dependent and kainic acid-lesioned rat brains. In: Adv. Biochem. Psychopharmacol. 18 (E. Costa and M. Trabucchi, eds.), Raven, pp. 161-173, 1978.
J.T. Coyle, K. Biziere and R. Schwarcz: Neurotoxicity of excitatory amino acids in the neural retina. In: Kainic Acid as a Tool in Neurobiology (E.G. McGeer, J.W. Olney and P.L. McGeer, eds.), Raven, pp. 177-188, 1978.
J.T. Coyle, E.G. McGeer, P.L. McGeer and R. Schwarcz: Neostriatal injections: a model for Huntington's chorea. In: Kainic Acid as a Tool in Neurobiology (E.G. McGeer, J.W. Olney and P.L. McGeer, eds.), Raven, pp. 139-160, 1978.
S.-O. Ögren, K. Fuxe, C. Köhler and R. Schwarcz: The interaction between brain noradrenaline and the pituitary adrenal axis in avoidance learning. In: Catecholamines: Basic and Clinical Frontiers (E. Usdin, I.J. Kopin and J. Barchas, eds.), Pergamon, pp. 1720-1722, 1979.
R. Schwarcz, K. Fuxe, K. Andersson and L. Ferland: ß-Endorphin and metenkephalin induced changes in amine turnover in discrete dopaminergic nerve terminal systems of the neostriatum and the limbic forebrain. In: Catecholamines: Basic and Clinical Frontiers (E. Usdin, I.J. Kopin and J. Barchas, eds.), Pergamon, pp. 1047-1049, 1979.
J.T. Coyle, K. Biziere, P. Campochiaro, E. London, R. Schwarcz and R. Zaczek: An animal model for Huntington's disease: striatal kainic acid lesion. In: Catecholamines: Basic and Clinical Frontiers (E. Usdin, I.J. Kopin and J. Barchas, eds.), Pergamon, pp. 1608-1610, 1979.
K. Fuxe, P. Bolme, G. Jonsson, L.F. Agnati, M. Goldstein, T. Hökfelt, R. Schwarcz and J. Engel: On the cardiovascular role of noradrenaline, adrenaline and peptide containing neuron systems in the brain. In: Perspectives in Nephrology and Hypertension (H. Schmitt and P. Meyers, eds.), Wiley, pp. 1-17, 1979.
K. Fuxe, K. Andersson, S.-O. Ögren, M. Perez de la Mora, R. Schwarcz, T. Hökfelt, P. Eneroth, J.-Å. Gustafsson and P. Skett: GABA neurons and their interaction with monoamine neurons. An anatomical, pharmacological and functional analysis. In: GABA Neurotransmitters (P. Krogsgaard-Larsen, J. Scheel-Krüger and H. Kofod, eds.), Munksgaard, pp. 74-94, 1979.
J.T. Coyle, K. Biziere, P. Campochiaro, R. Schwarcz and R. Zaczek: Kainic acid induced lesion of the striatum as an animal model for Huntington's disease. In: GABA Neurotransmitters (P. Krogsgaard-Larsen, J. Scheel Krüger and H. Kofod, eds.), Munksgaard, pp. 419-431, 1979
K. Fuxe, K. Andersson, A. Löfström, T. Hökfelt, L. Ferland, L.F. Agnati, M. Perez de la Mora, R. Schwarcz, P. Eneroth, J.-Å. Gustafsson and P. Skett: Neurotransmitters mechanisms in the control of the secretion of hormones from the anterior pituitary. In: Central Regulation of the Endocrine System, Nobel Symposium 42 (K. Fuxe, T. Hökfelt and R. Luft, eds.), Plenum, pp. 349-380, 1979.
K. Fuxe, K. Andersson, R. Schwarcz, L.F. Agnati, M. Perez de la Mora, T. Hökfelt, M. Goldstein, L. Ferland, L. Possani and R. Tapia: Studies on different types of dopamine nerve terminals in the forebrain and their possible interactions with neurons containing GABA, glutamate and opioid hormones and with hormones. In: Adv. Neurol. 24 (L.J. Poirier, T.L Sourkes and P.J. Bedard, eds.), Raven, pp. 199-215, 1979.
R. Schwarcz, C. Köhler, K. Fuxe, T. Hökfelt and M. Goldstein: On the mechanism of selective neuronal degeneration in the rat brain: studies with ibotenic acid. In: Adv. Neurol. 23 (T.N. Chase, N. Wexler and A. Barbeau, eds.), Raven, pp. 655-668, 1979.
R. Schwarcz, K. Fuxe, T. Hökfelt, K. Andersson and J.T. Coyle: Dopamine and Huntington's disease: assessment using the kainic acid model. In: Dopaminergic Ergot Derivatives and Motor Function (K. Fuxe and D.B. Calne, eds.), Pergamon, pp. 115-126, 1979.
K. Fuxe, R. Schwarcz, L. Agnati, B. Fredholm, S.-O. Ögren, C. Köhler and J.-Å. Gustafsson: Actions of ergot derivatives at dopamine synapses. In: Dopaminergic Ergot Derivatives and Motor Function (K. Fuxe and D.B. Calne, eds.), Pergamon, pp. 141-157, 1979.
K. Fuxe, S.-O. Ögren, H. Hall, L.F. Agnati, K. Andersson, C. Köhler and R. Schwarcz: Effects of chronic treatment with L-sulpiride and haloperidol on central monoaminergic mechanisms. In: Long-term Effects of Neuroleptics, (F. Cattabeni, G. Racagni, P.F. Spano and E. Costa, eds.), Raven, pp. 193-206, 1980.
T. Hökfelt, O. Johansson, Å. Ljungdahl, J.M. Lundberg, M. Schultzberg, K. Fuxe, L. Skirboll, R. Schwarcz and M. Goldstein: Peptidergic neurons in the nervous system with special reference to the extrapyramidal system: Morphological and functional aspects. In: Parkinson's Disease - Current Progress, Problems and Management (U.K. Rinne, M. Klinger and G. Stamm, eds.), Elsevier, pp. 29-48, 1980.
R. Schwarcz, C. Köhler, R.M. Mangano and A.N. Neophytides: Glutamate induced neuronal degeneration: Studies on the role of glutamate re-uptake. In: Glutamate as a Neurotransmitter (G. Di Chiara and G.L. Gessa, eds.), Raven, pp. 403-412, 1981.
J.T. Coyle and R. Schwarcz: The use of excitatory amino acids as selective neurotoxins. In: Handbook of Chemical Neuroanatomy, volume 1 (A. Björklund and T. Hökfelt, eds.), Elsevier, pp. 508-527, 1983.
R. Schwarcz, W.O. Whetsell Jr. and A.C. Foster: The neurodegenerative properties of intracerebral quinolinic acid and its structural analog cis-2,3-piperidine dicarboxylic acid. In: Excitotoxins (K. Fuxe, P.J. Roberts and R. Schwarcz, eds.), Macmillan, pp. 122-137, 1983.
W.O. Whetsell Jr. and R. Schwarcz: Mechanisms of excitotoxins examined in organotypic cultures of rat central nervous system. In: Excitotoxins (K. Fuxe, P.J. Roberts and R. Schwarcz, eds.), Macmillan, pp. 207-219, 1983.
K. Fuxe, L.F. Agnati, P. Frey, C. Köhler, M.F. Celani, K. Andersson, N. Battistini, C. Farabegoli and R. Schwarcz: Ibotenate as a tool in neurobiology: studies on dopaminergic and cholecystokinin immunoreactive neurons after ibotenate induced lesions. In: Excitotoxins (K. Fuxe, P.J. Roberts and R. Schwarcz, eds.), Macmillan, pp. 223-238, 1983.
R. Schwarcz and A.C. Foster: Studies on quinolinic acid metabolism in rat brain. Clin. Neuropharmacol., 7, Suppl. 1, 450-451, 1984.
C. Aldinio, S. Mazzari, G. Toffano and R. Schwarcz: Effects of intracerebral quinolinic acid injections on serotonergic neurons. Clin. Neuropharmacol., 7, Suppl. 1, 454-455, 1984.
E.D. French, A.C. Foster, A. Vezzani and R. Schwarcz: Quinolinate and kynurenate, two endogenous tryptophan metabolites with potential links to epileptic disorders. Clin. Neuropharmacol., 7, Suppl. 1, 456-457, 1984.
R. Schwarcz, A. Vezzani and E.D. French: Quinolinic acid-induced seizures and hippocampal nerve cell loss: antagonism by -APH and kynurenic acid. In: Workshop on Neurotransmitters in Epilepsy III (G. Nistico, P.L. Morselli, K.G. Lloyd, R.G. Fariello and J. Engel, Jr., eds.), Raven, pp. 247-257, 1986.
E.D. French, A. Vezzani, W.O. Whetsell Jr. and R. Schwarcz: Antiexcitotoxic actions of taurine in the rat hippocampus studied in vivo and in vitro. In: Excitatory Amino Acids and Epilepsy (R. Schwarcz and Y. Ben-Ari, eds.), Plenum, pp. 349-362, 1986.
R. Schwarcz, C. Speciale, E. Okuno, E.D. French and C. Köhler: Quinolinic acid: a pathogen in seizure disorders? In: Excitatory Amino Acids and Epilepsy (R. Schwarcz and Y. Ben-Ari, eds.), Plenum, pp. 697-707, 1986.
R. Schwarcz, E. Okuno and C. Köhler: Endogenous excitotoxins: focus on quinolinic acid. In: Excitatory Amino Acid Neurotransmitters (P.J. Roberts, J. Storm-Mathisen and H.F. Bradford, eds.), Macmillan, pp. 381-396, 1986.
R. Schwarcz, E. Okuno, C. Speciale, W.O. Whetsell Jr. and C. Köhler: Neuronal degeneration in animals and man: the quinolinic acid connection. In: Neurotoxins and their Pharmacological Implications (P.G. Jenner, ed.), Raven, pp. 19-32, 1987.
R. Schwarcz and I. Shoulson: Excitotoxins and Huntington's disease. In: Animal Models of Dementia: A Synaptic Neurochemical Perspective (J.T. Coyle, ed.), Alan Liss, pp. 39-68, 1987.
W.O. Whetsell Jr., C. Köhler and R. Schwarcz: Quinolinic acid: a glia-derived excitotoxin in the mammalian central nervous system. In: Biochemical Pathology of Astrocytes (M.D. Norenberg, L. Hertz and A. Schousboe, eds.), Alan R. Liss, pp. 191-202, 1988.
R. Schwarcz, C. Speciale, J.B.P. Gramsbergen and W.A. Turski: Kynurenines in the mammalian brain. In: Frontiers in Excitatory Amino Acid Research (E.A. Cavalheiro, J. Lehmann and L. Turski, eds.) Alan R. Liss, pp. 613-620, 1988.
R. Schwarcz, W.O. Whetsell Jr. and W.A. Turski: Kynurenines and nerve cell death. In: Neurodegenerative Disorders: the Role Played by Endotoxins and Xenobiotics (G. Nappi, O. Hornykiewicz, R.G. Fariello, A. Agnoli and H. Klawans, eds.), Raven, pp. 7-22, 1988.
C. Köhler, E. Okuno and R. Schwarcz: Quinolinic acid metabolism in the brain: biochemical and immunohistochemical analysis. In: Quinolinic Acid and other Kynurenines (T.W. Stone, ed.), CRC Press, pp. 63-76, 1988.
A.C. Foster and R. Schwarcz: Neurotoxic effects of quinolinic acid in the central nervous system. In: Quinolinic acid and other Kynurenines (T.W. Stone, ed.), CRC Press, pp. 173-192, 1988.
R. Schwarcz, C. Speciale and W.A. Turski: Kynurenines, glia, and the pathogenesis of neurodegenerative disorders. In: Parkinsonism and Aging (D.B. Calne, G. Comi, D. Crippa, R. Horowski and M. Trabucchi, eds.), Raven, pp. 97-105, 1989.
R. Schwarcz and D.L. Price: The role of excitotoxins in experimental systems and in human neurological disorders. In: Neurodegenerative Disorders: Mechanisms and Prospects for Therapy (D.L. Price, H. Thoenen and A.J. Aguayo, eds.), Wiley, pp. 21-34, 1991.
R. Schwarcz, H. Baran, H.-Q. Wu, F. Du and O. McMaster: The neurochemistry of quinolinate and kynurenate: current concepts. In: Excitatory Amino Acids (B.S. Meldrum, F. Moroni, R.P. Simon and J.H. Woods, eds.), Raven, pp. 367-375, 1991.
R. Schwarcz and F. Du: Quinolinic acid and kynurenic acid in the mammalian brain. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young and R.R. Brown, eds.), Plenum, pp. 185-199, 1991.
H. Baran and R. Schwarcz: Evidence for the preferential production of 3-hydroxyanthranilic acid from anthranilic acid in the rat brain. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young and R.R. Brown, eds.), Plenum, pp. 485-488, 1991.
J.L. Walsh, W.P. Todd, B.K. Carpenter and R. Schwarcz: 4-Halo-3-hydroxyanthranilates are potent inhibitors of 3-hydroxyanthranilate oxygenase in the rat brain in vitro and in vivo. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young and R.R. Brown, eds.), Plenum, pp. 579-582, 1991.
C. Speciale and R. Schwarcz: On the disposition of de novo synthesized quinolinic acid in rat brain tissue. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young, and R.R. Brown, eds.), Plenum, pp. 583-586, 1991.
J.B.P. Gramsbergen, W.A. Turski and R. Schwarcz: Brain-specific control of kynurenic acid production by depolarizing agents. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young and R.R. Brown, eds.), Plenum, pp. 587-590, 1991.
A. Vezzani, J.B.P. Gramsbergen, C. Speciale and R. Schwarcz: Production of quinolinic acid and kynurenic acid by human glioma. In: Kynurenine and Serotonin Pathways: Progress in Tryptophan Research (R. Schwarcz, S.N. Young and R.R. Brown, eds.), Plenum, pp. 691-695, 1991.
R. Schwarcz: Excitotoxins, kynurenines and neuropsychiatric diseases: Implications for drug development. In: Drug Research Related to Neuroactive Amino Acids (A. Schoesboe, N.H. Diemer and H. Kofod, eds.), Munksgaard, Copenhagen, pp. 287-301, 1992.
R. Schwarcz, F. Du, W. Schmidt, W.A. Turski, J.B.P. Gramsbergen, E. Okuno and R.C. Roberts: Kynurenic acid: a potential pathogen in brain disorders. In: Neurotoxins and Neurodegenerative Disease, volume 648 (J.W. Langston and A. Young, eds.), Ann. N.Y. Acad. Sci., pp. 140-153, 1992.
R. Schwarcz, H.-Q. Wu, P.D. Shepard and R.C. Roberts: Astrocytic kynurenines as modulators of dopaminergic function in the rat basal ganglia. In: Trophic Regulation of the Basal Ganglia: Focus on Dopamine (K. Fuxe, L.F. Agnati, B. Bjelke and D. Ottoson, eds.), Pergamon, pp. 365-379, 1994.
R. Schwarcz, P. Guidetti and R.C. Roberts: Quinolinic acid and kynurenic acid: glia-derived modulators of excitotoxic brain injury. In: The Role of Glia in Neurotoxicity (M. Aschner and H.K. Kimelberg, eds.), CRC Press, pp. 245-262, 1996.
R. Schwarcz, G. Ceresoli and P. Guidetti: Kynurenine metabolism in the rat brain in vivo: effect of acute excitotoxic insults. In: Recent Advances in Tryptophan Research (G. Allegri Filippini and C.V.L. Costa, eds.), Plenum, pp. 211-219, 1996.
C. Speciale, M. Cini, H.-Q. Wu, P. Salvati, R. Schwarcz, A. Molinari and M. Varasi: Kynurenic acid-enhancing and anti-ischemic effects of the potent kynurenine 3-hydroxylase inhibitor FCE 28833 in rodents. In: Recent Advances in Tryptophan Research (G. Allegri Filippini, C.V.L. Costa and A. Bertazzo, eds.), Plenum, pp. 221-227, 1996.
L. Curatolo, C. Caccia, C. Speciale, L. Raimondi, M. Cini, M. Marconi, A. Molinari and R. Schwarcz: Modulation of extracellular kynurenic acid content by excitatory amino acids in primary cultures of rat astrocytes. In: Recent Advances in Tryptophan Research (G. Allegri Filippini and C.V.L. Costa, eds.), Plenum, pp. 273-276, 1996.
M. Mosca, L. Cozzi, J. Breton, N. Avanzi, S. Toma, E. Okuno, R. Schwarcz, C. Speciale, S. Magagnin, M. Mostardini and L. Benatti: Cloning of rat and human kynurenine aminotransferase. In: Recent Advances in Tryptophan Research (G. Allegri Filippini and C.V.L. Costa, eds.), Plenum, pp. 449-454, 1996.
A. Giordani, L. Corti, M. Cini, M. Marconi, A. Pillan, R. Ferrario, R. Schwarcz, P. Guidetti, C. Speciale and M. Varasi: Benzoylalanine analogues as inhibitors of rat brain kynureninase and kynurenine 3-hydroxylase. In: Recent Advances in Tryptophan Research (G. Allegri Filippini and C.V.L. Costa, eds.), Plenum, pp. 499-505, 1996.
R. Schwarcz, G. Ceresoli-Borroni, H.-Q. Wu, A. Rassoulpour, B. Poeggeler, P.S. Hodgkins and P. Guidetti: Modulation and function of kynurenic acid in the immature rat brain. In: Tryptophan, Serotonin, Melatonin - Basic Aspects and Applications (G. Huether, W. Kochen, T.J. Simat and H. Steinhart, eds.), Plenum, pp. 113-123, 1999.
R. Schwarcz, T. Eid and F. Du: Neurons in layer III of the entorhinal cortex: a role in epileptogenesis and epilepsy? In: The Parahippocampal Region: Implications for Neurological and Psychiatric Diseases, volume 911 (H.E. Scharfman, M.P. Witter and R. Schwarcz, eds.), Ann. N.Y. Acad. Sci., pp. 328-342, 2000.
R. Schwarcz, H.E. Scharfman and E.H. Bertram: Temporal lobe epilepsy: renewed emphasis on extrahippocampal areas. In: ACNP, 5th Generation of Progress (K.L. Davis, D. Charney, J.T.Coyle and C.Nemeroff, eds.), Lippincott Williams and Wilkins, pp. 1843-1856, 2002.
R. Schwarcz and R.L. Albin: Huntington’s Disease. In: Ionotropic Glutamate Receptors as Therapeutic Targets (D. Lodge, W. Danysz and C.G. Parsons, eds.), Graham Publishing Group, pp. 587-610, 2002.
P. Guidetti and R. Schwarcz: 3-Hydroxykynurenine and quinolinate: pathogenic synergism in early grade Huntington’s Disease? In: Developments in Tryptophan and Serotonin Metabolism (G. Allegri, C.V.L. Costa, E. Ragazzi, H. Steinhardt and L. Varesio, eds.), Kluwer, pp. 137-145, 2003.
H.E. Scharfman and R. Schwarcz: Neuromodulation of seizures, epileptogenesis, and epilepsy. In: Epilepsy: a Comprehensive Textbook (2nd edition) (J. Engel and T.A. Pedley, eds.), Lippincott Williams & Wilkins, pp. 289-306, 2007.
R.S. Sloviter, A.V. Bumanglag, R. Schwarcz and M. Frotscher: Abnormal dentate gyrus network circuitry in temporal lobe epilepsy. In: Jasper’s Basic Mechanisms of the Epilepsies – Fourth Edition (J.L. Noebels, M. Avoli, M.A. Rogawski, R.W. Olsen and A.V. Delgado-Escueta, eds.), Oxford, pp. 354-369, 2012.
R. Schwarcz: Kynurenines: poor relatives no more. In: Targeting the Broadly Pathogenic Kynurenine Pathway (S. Mittal, ed.), pp. VII-IX, Springer, 2015.
A. Pocivavsek, F.M. Notarangelo, H.-Q. Wu, J.P. Bruno and R. Schwarcz: Astrocytes as pharmacological targets in the treatment of schizophrenia: focus on kynurenic acid. In: Modeling the Psychopathological Dimensions of Schizophrenia. Handbooks of Behavioral Neuroscience, volume 23 (M. Pletnikov and J. Waddington, eds.), Elsevier, pp. 423-443, 2016.
R. Schwarcz: Kynurenines and glutamate: multiple links and therapeutic implications. In: Neuropsychopharmacology: a Tribute to Joseph T. Coyle, Advances in Pharmacology, volume 76 (R. Schwarcz, ed.), Elsevier, pp. 13-37, 2016.
K.V. Sathyasaikumar, C. Breda, R. Schwarcz and F. Giorgini: Assessing and modulating kynurenine pathway dynamics in Huntington’s disease: focus on kynurenine 3-monooxygenase. In: Huntington’s Disease: Methods and Protocols, Methods in Molecular Biology, volume 1780 (S.V. Precious, A.E. Rosser and S.B. Dunnett, eds.), Springer, pp. 397-413, 2018.
R. Schwarcz and S. Erhardt: Kynurenic acid in brain function and dysfunction: focus on the pathophysiology and treatment of schizophrenia. In: Dimensions of Psychosis: Comprehensive Conceptualization and Treatments (C.A. Tamminga, E.I. Ivleva, U. Reininghaus and J. van Os, eds.), Oxford University Press, pp. 323-331, 2020.
Clinical Specialty Details
Epilepsy, Huntington's disease, Parkinson's disease, Major depressive disorders, Schizophrenia
Awards and Affiliations
1972 - 1974: Research Assistant, Institute of General Biochemistry, Vienna, Austria
1975 - 1977: Postdoctoral Fellow with J.T. Coyle, M.D., Department of Pharmacology, Johns Hopkins University, Baltimore, Maryland, USA
1977 - 1979: Postdoctoral Fellow with K. Fuxe, M.D., Department of Histology, Karolinska Institute, Stockholm, Sweden
1979 - 1982: Assistant Professor of Psychiatry, Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore,
Maryland, USA
1982 - 1986: Associate Professor of Psychiatry, Maryland Psychiatric Research Center
1986 - : Professor of Psychiatry, Maryland Psychiatric Research Center
1986 - : Professor of Pharmacology, University of Maryland School of Medicine
2000 - : Professor of Pediatrics, University of Maryland School of Medicine
2009- : Adjunct Professor (elected; re-elected 2015 and 2021), Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
Friedrich Merz Professor, University of Frankfurt, Germany (1993)
Merck Neuroscience Lecturer, British Pharmacological Society (1994)
Faculty Researcher of the Year, University of Maryland (1997)
4th Hillarp Lecture, Society for Neuroscience (1998)
Visiting Professor, University of Perugia, Italy (2000, 2007)
Dezsö Miskolczy Memorial Lecturer, University of Szeged, Hungary (2001)
ASPET Epilepsy Research Award (2007)
University System of Maryland Regents’ Faculty Award (2007)
Musajo Medal – International Tryptophan Society (2015)
Grants and Contracts
1. "Platelets, Glutamate and Huntington's Disease": 11/1/79 - 12/31/80; The Wills Foundation; $15,000.
2. "Kainic Acid and Striatal Dopamine Turnover": 01/01/80 - 12/31/80; NIMH small grant; $10,638.
3. "Properties of Synthetic and Degradative Enzymes for Glutamate in HD": 7/1/80 - 12/31/81; The Wills Foundation; $15,000.
4. "Neuroexcitatory Amino Acid Mechanisms in vivo and in vitro": 1/1/81 - 12/31/83; NINCDS grant; $149,550.
5. "Kainic Acid, Hippocampus and Temporal Lobe Epilepsy": 8/1/81 - 7/31/84; NINCDS grant; $137,515.
6. "GMl and Hippocampal Lesions": 8/1/82 - 7/31/85; FIDIA Research Laboratories; $31,330.
7. "Excitotoxic Amino Acids: Antagonism in vivo and in vitro": 2/1/83 - 1/31/85; NATO grant for international collaboration in research; $10,400.
8. "Synthesis of (-)2-Amino-7-Phosphonoheptanoic Acid": 4/1/83 - 6/30/83; Committee to Combat Huntington's Disease; $5,000.
9. "Neuroexcitatory Amino Acid Mechanisms in vivo and in vitro": 1/1/84 - 12/31/86; NINCDS grant; $265,450.
10. "Quinolinic Acid and Seizure Disorders" 8/1/84 - 7/31/87; NINCDS grant; $209,417.
11. "Quinolinic Acid and Parkinson's Disease": 7/1/85 - 6/30/86; American Parkinson Disease Association; $20,000.
12. "Quinolinic Acid and Parkinson's Disease/II": 7/1/86 - 6/30/87; American Parkinson Disease Association: $20,000.
13. "Neuroexcitatory Amino Acid Mechanisms in vivo and in vitro": 1/1/87 - 12/31/89; NINCDS grant; $504,613.
14. "Quinolinic Acid and Seizure Disorders": 8/1/87 - 7/31/90; NINCDS grant; $335,643.
15. "NeuroscienceCenter for Research in Schizophrenia" (W.T. Carpenter, P.I.); subproject "Neuroleptic Treatment and Brain Kynurenines": 3/1/89 - 2/28/94; NIMH grant;
$220,000.
16. "Quinolinic Acid and Seizure Disorders": 9/24/90 - 9/23/93; NINDS grant; $601,502.
17. "Neuroexcitatory Amino Acid Mechanisms in vivo and in vitro": 1/1/90 - 12/31/94; NINDS grant; $1,187,086.
18. "Neuroactive Kynurenines": 1/1/92 - 12/31/94; Pharmacia/Farmitalia (Milano); $304,500.
19. "Quinolinate Synthesis Inhibitors": 1/1/91 - 12/31/94; ASTRA ArcusAB (Södertälje); $114,333.
20. "Neuroactive Kynurenines": 1/1/95 - 12/31/95; Pharmacia (Milano); $150,000.
21. "Neuroactive Kynurenines": 1/1/96 - 12/31/96; Pharmacia (Milano); $150,000.
22. "Kynurenines, Glia and Epilepsy": 4/1/94 - 1/31/98; NINDS grant; $926,068.
23. "Neuroactive Kynurenines": 1/1/97 - 12/31/97; Pharmacia & Upjohn (Milano); $150,000.
24. "Neuroexcitatory Amino Acid Mechanisms in vivo and in vitro": 1/1/95 - 12/31/99; NINDS grant; $1,069,605.
25. "Kynurenines, Glia and Epilepsy": 2/1/98 - 1/31/03; NINDS grant; $1,027,158.
26. "Metabolic and Developmental Aspects of Mental Retardation" (H.R. Zielke, P.I.); subproject "Kynurenic Acid Formation & Function During Development": 5/1/98 -
4/30/03; NICHD grant; $513,665.
27. “Kynurenic Acid, Nicotine and Schizophrenia”: 5/1/02 - 4/30/03; NARSAD Distinguished Investigator grant; $99,746.
28. “The Role of Kynurenic Acid in Development”: 5/1/01 - 7/1/03; NRSA grant; $50,933.
29. “Kynurenine 3-hydroxylase as a Target for Drug Development”: 11/1/01 - 10/31/03; Newron (Milano); $170,000.
30. “Quinolinic Acid in HD Mouse models”: 4/1/04 – 9/30/04; HighQ-Hereditary Disease Foundation; $67,500.
31. “Chronic Interventions to Influence Brain Kynurenine Pathway Metabolism in Mice”: 7/1/05-12/31/05; HighQ Foundation; $74,500.
32. “Kynurenic Acid Synthesis and Schizophrenia”: 7/1/05-3/31/08; Mitsubishi Pharma; $185,000.
33. “Nicotinic Receptor: Role in Hippocampal Synaptic Function” (E.X. Albuquerque, P.I.): 8/1/02-7/31/07; NINDS grant; $200,000.
34. "Kynurenines, Glia and Epilepsy”: 7/1/03 - 6/30/07; NINDS grant; $1,160,168.
35. “Imaging Tryptophan Metabolism in Children with Epilepsy” (D.C. Chugani, P.I.): 12/01/03-11/30/08; NINDS grant; $66,000.
36. "Metabolic and Developmental Aspects of Mental Retardation" (H.R. Zielke, P.I.); subproject "Kynurenic Acid Formation & Function During Development":
4/1/04-3/31/09; NICHD grant; $675,000.
37. “The Kynurenine Pathway in Huntington’s Disease”: 11/01/06-10/31/08; HighQ Foundation; $550,000.
38. “Kynurenine Pathway Metabolism: In Vivo Drug Effects”: 5/15/08-5/14/09; CHDI Inc.; $110,402.
39. “Kynurenic Acid Synthesis and Schizophrenia”: 9/1/08-8/31/09; Mitsubishi-Tanabe; $85,000.
40. “Kynurenine Pathway Enzymes in the Human Brain in Huntington’s Disease”: 9/1/09-8/31/10; CHDI Inc.; $175,853.
41. “Understanding Effects of Chronically Manipulated Brain Kynurenate Levels on Neural Systems”: 9/1/09-8/31/10; Mitsubishi-Tanabe; $95,000.
42. “Validation of KAT II as a Therapeutic Target for Schizophrenia”: 7/1/2010- 6/30/2012; Bristol-Myers-Squibb Innovation grant; $230,000.
43. “Understanding Effects of Neurochemical Consequences Caused by Systemic Manipulation of the Brain Kynurenine Pathway from Viewpoints of Psychiatric
Symptoms”: 8/1/10-3/31/13; Mitsubishi-Tanabe; $275,000.
44. ”The Role of Microglia and the Kynurenine Pathway in Huntington’s Disease" (co-P.I. with P.J. Muchowski): 3/1/09-2/28/14; NINDS grant; $625,000.
45. “Proteopathies of the Aging Central Nervous System“ (L. Mucke, P.I.); subproject “Kynurenines, Microglia and Alzheimer’s Disease” (co-P.I. with P.J. Muchowski):
8/1/08-7/31/13; NIA grant; $265,000.
46. “Nicotinic Receptor: Role in Hippocampal Synaptic Function” (co-P.I. with E.X. Albuquerque): 8/1/08-7/31/13; NINDS grant; $337,500.
47. “Endogenous Kynurenic Acid Modulates Prefrontal ACh Levels and Cognitive Behavior” (co-P.I. with J.P. Bruno): 12/1/09-11/30/14; NIMH grant; $1,250,000.
48. “An NMDA Glycine Site Antagonist for the Treatment of Major Depressive Disorder” (co-P.I. with T.D. Gould): 9/9/13-9/8/15; NIMH grant; $275,000.
49. “Development of Novel, Systemically Active KAT II Inhibitors”: 3/1/2014 - 2/28/2016; Mitsubishi-Pharma; $200,000.
50. “Inflammation, Kynurenines and Psychiatric Diseases”: 9/1/13-8/31/16; Lundbeck Research USA; $708,000.
51. “Kynurenic Acid and Cognitive Abnormalities in Schizophrenia”: 6/11/2015- 6/10/2016; NIMH Supplement sex differences (Conte Center); $100,000.
52. “Kynurenic Acid and Cognitive Abnormalities in Schizophrenia”: 4/1/2014-3/31/2019; NIMH grant (ConteCenter); $10,712,744.
53. “Kynurenic Acid and Cognitive Abnormalities in Schizophrenia”: 6/1/2017-3/31/2019; NIMH Supplement NeuroBioBank (Conte Center); $206,000.
54. “4-Cl-Kynurenine (AV-101) vs. Kynurenine: Effects on Neurogenesis inthe Rat Brain“: 7/1/2017-6/30/2018; VistaGen Therapeutics; $146,826.
55. “Kynurenic Acid and Cognitive Abnormalities in Schizophrenia”: 6/1/2017-3/31/2019; NIMH Supplement NeuroBioBank (Conte Center); $206,000.
56. “Kynurenic Acid and Cognitive Abnormalities in Schizophrenia”: 9/11/2019-6/30/2024; NIMH grant (Conte Center); $14,224,949.
In the News
United States Patents (+ year of original filing)
1. "Aminoacid Isomers, their Production and their Medicinal Use" (with J.F. Collins and K. Curry) (1981) US Patent 4,483,853 (issued November 20, 1984)
2. "NMDA Antagonists" (with M. G. Palfreyman, I.A. McDonald, F. G. Salituro and B.M. Baron) (1991) US Patent 5,470,870 (issued November 28, 1995)
3. “New Compounds” (with S.K.M. Björk, B.K. Carpenter, B.K. Gotthammar, M.T. Linderberg, J.P. Luthman and K.M.I. Persson) (1994) US Patent 5,523,475 (issued June 4, 1996)
4. “3-Hydroxyanthranilic Acid Derivatives” (with S.K.M. Björk, B.K. Gotthammar, M.T. Linderberg, J.P. Luthman and K.M.I. Persson) (1995) US Patent 5,661,183 (issued August 26, 1997)
5. “Compounds” (with S.K.M. Björk, B.K. Gotthammar, M.T. Linderberg, J.P. Luthman and K.M.I. Persson) (1996) US Patent 5,688,945 (issued November 18, 1997)
6. "Substituted Kynurenines and Process for their Preparation" (with M. Varasi, A. Della Torre, C. Speciale and A. Bianchetti) (1995) US Patent 5,786,508 (issued July 28, 1998)
7. "Hydroxylated Anthranilic Acid Derivatives" (with S.K.M. Björk, B.K. Gotthammar, M.T. Linderberg, J.P. Luthman, K.M.I. Persson and B.K. Carpenter) (1995) US Patent 5,883,129 (issued March 15, 1999)
8. "Recombinant KAT Enzyme and Process for its Preparation" (with L. Benatti, J. Breton, C. Speciale, E. Okuno and M. Mosca) (1997) U.S. Patent 6,136,572 (issued October 24, 2000)
9. “4-Sulfonyl-substituted Benzoylalanine Derivatives Useful as Kynurenine-Aminotransferase Inhibitors” (with R. Pellicciari and P. Guidetti) (2004)
10. “Small Inhibitors of Kynurenine 3-Monooxygenase” (with P.J. Muchowski, J.M. Muchowski and P. Guidetti) (2007) U.S. Patent 7,994,338 (issued August 9, 2011)
11. “Kynurenine Aminotransferase Inhibitors” (with Y. Kajii) (2007)
12. “Inhibitors of Kynurenine Aminotransferase and Uses Therefor" (with P. Guidetti and R. Pellicciari) (2007)
13. “Small Molecule Inhibitors of Kynurenine 3-Monooxygenase” (with P.J. Muchowski and J.M. Muchowski) (2011) U.S. Patent 8,710,237 (issued April 29, 2014)
14. “A New Class of 3-Hydroxyanthranilate-3,4-dioxygenase (3-HAO) Inhibitors as Potential Neuroprotective Drugs” (with G. Costantino) (2011) United States Patent 9,260,394 (issued February 16, 2016)
15. "Derivatives of Nicotinic Acid N-Oxide, Their Preparation and Their Use as Inhibitors of Enzyme 3-Hydroxyanthranilate-3, 4-Dioxygenase" (with G. Costantino and L. Amori) (2015) United States Patent 9,487,486 (issued November 8, 2016)
Professional Activity
Editorial Boards, National and International Councils/Committees:
"Neuropharmacology" (1987-1993)
"Current CNS Patents" (1990- )
"Journal of Neural Transmission" (1996-2006)
"Amino Acids" (1997-2009)
“Current Drug Targets - CNS and Neurological Disorders” (1999- )
“Medicinal Chemistry Reviews” (2003- )
“Schizophrenia Bulletin” (2005-2010)
“International Journal of Tryptophan Research” (2008- )
“Frontiers in Molecular Psychiatry” (2010- )
Scientific Council, Huntington's Disease Society of America (1987-1993)
Council, International Study Group for Tryptophan Research (1987-1998)
Member, Neurological Sciences 2, NINDS Study Section (1990-1994)
Member, Investigator's Workshop Committee, American Epilepsy Society (1994-1997)
NIH Reviewer's Reserve (1994-1998)
Scientific Advisory Committee, Huntington's Study Group for drug development (1994- 1998)
Advisory Board, Vienna Brain Research Institute (Chair) (1995-2000)
Member, Research Recognition Awards Committee, American Epilepsy Society (1999-2001)
Member, Lennox Award Committee, American Epilepsy Society (1999-2001) (Chair, 2001)
Member, ACNP Award Committee (2001)
Member, ACNP Program Committee (2002-2004)
Artemis Neuroscience, Inc., Scientific Advisory Board (Chair) (2002-2003)
Vistagen, Inc., Scientific Advisory Board (2003- )
Member, Otto-Loewi-Preis Committee, Austrian Neuroscience Association (2005)
Member, International Review Board, Vienna Brain Research Institute (2005- )
Member, ACNP Program Committee (2006-2008; Co-Chair, 2006, Chair, 2007)
Member, Program Committee, American Epilepsy Society (2007-2008)
Member, Research Initiative Fund Review Committee, American Epilepsy Society (2007-2009)
Board of Trustees, Medical University of Vienna (2008-2018)
Member, ACNP Liaison Committee with Government Agencies and the Pharmaceutical Industry (2009-2011)
Member, Scientific Council, National Alliance for Research on Schizophrenia and Depression (NARSAD) (2009- )
Member, ACNP Ethics Committee (2012-2015)
Member, ACNP Honorific Awards Committee (2016)
Member, International Scientific Advisory Board, Medical University of Vienna (2019-2024)
Lab Techniques and Equipment
Focus on: Biochemistry, Pharmacology, Histology, Behavior
Worldwide net of collaborators with complementary, state-of-the art analytical methodologies/instrumentaion