Targeting kynurenine aminotransferase II in psychiatric diseases: Promising effects of an orally active enzyme inhibitor

Schizophrenia Bulletin

Volumn 40, Issue SUPPL. 2, 2014, Pages

  Wu, Hui Qiu ^a   Okuyama, Masahiro ^b   Kajii, Yasushi ^b,d   Pocivavsek, Ana ^a   Bruno, John P ^c   Schwarcz, Robert ^a  

^a UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^b MITSUBISHI TANABE PHARMA CORPORATION   (Japan)

^c OHIO STATE UNIVERSITY   (United States)

^d ABBVIE INC   (United States)

Author keywords

kynurenic acid; microdialysis; Morris water maze; schizophrenia; spatial memory

Indexed keywords

BFF 816; ENZYME INHIBITOR; GLUTAMIC ACID; KYNURENINE AMINOTRANSFERASE; UNCLASSIFIED DRUG; AMINOTRANSFERASE; KYNURENINE-OXOGLUTARATE TRANSAMINASE;

ANIMAL EXPERIMENT; ARTICLE; BEHAVIOR CHANGE; BRAIN REGION; CHOLINERGIC ACTIVITY; CONTROLLED STUDY; DOPAMINERGIC ACTIVITY; DRUG EFFECT; ENZYME INHIBITION; EXTRACELLULAR SPACE; MALE; MENTAL DISEASE; MICRODIALYSIS; MORRIS WATER MAZE TEST; NEUROBIOLOGY; NEUROPHYSIOLOGY; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RAT; SPATIAL MEMORY; TASK PERFORMANCE; ANIMAL; ANIMAL BEHAVIOR; ANTAGONISTS AND INHIBITORS; BRAIN; DRUG EFFECTS; MAZE TEST; SCHIZOPHRENIA; SPRAGUE DAWLEY RAT;

ANIMALS; BEHAVIOR, ANIMAL; BRAIN; ENZYME INHIBITORS; MALE; MAZE LEARNING; MICRODIALYSIS; RATS; RATS, SPRAGUE-DAWLEY; SCHIZOPHRENIA; TRANSAMINASES;

EID: 84895735874     PISSN: 05867614     EISSN: 17451701     Source Type: Journal    
DOI: 10.1093/schbul/sbt157     Document Type: Article

References (53)

1. Schwarcz R, Whetsell WO Jr, Mangano RM. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science. 1983;219:316-318.
2. Foster AC, Vezzani A, French ED, Schwarcz R. Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid. Neurosci Lett. 1984;48:273-278.
3. Schwarcz R, Foster AC, French ED, Whetsell WO Jr, Köhler C. Excitotoxic models for neurodegenerative disorders. Life Sci. 1984;35:19-32.
4. Davies J, Evans RH, Francis AA, Watkins JC. Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system. J Physiol (Paris). 1979;75:641-654.
5. Hall JG, Hicks TP, McLennan H, Richardson TL, Wheal HV. The excitation of mammalian central neurones by amino acids. J Physiol (Lond). 1979;286:29-39.
6. McLennan H. Receptors for the excitatory amino acids in the mammalian central nervous system. Prog Neurobiol. 1983;20:251-271.
7. Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller B. Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia. Neurosci Lett. 1980;20:379-382.
8. Collingridge GL, Kehl SJ, McLennan H. Excitatory amino acids in synaptic transmission in the Schaffer collateralcommussural pathway of the rat hippocampus. J Physiol. 1983;334:33-46.
9. Thomson AM, West DC, Lodge D. An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? Nature. 1985;313:479-481.
10. Allen RM, Young SJ. Phencyclidine-induced psychosis. Am J Psychiatry. 1978;135:1081-1084.
11. Javitt DC. Negative schizophrenic symptomatology and the PCP (phencyclidine) model of schizophrenia. Hillside J Clin Psychiatry. 1987;9:12-35.
12. Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methylaspartate. Br J Pharmacol. 1983;79:565-575.
13. Coyle JT. NMDA receptor and schizophrenia: a brief history. Schizophr Bull. 2012;38:920-926.
14. Tamminga CA. Schizophrenia and glutamatergic transmission. Crit Rev Neurobiol. 1998;12:21-36.
15. Carpenter WT Jr, Arango C, Buchanan RW, Kirkpatrick B. Deficit psychopathology and a paradigm shift in schizophrenia research. Biol Psychiatry. 1999;46:352-360.
16. Nuechterlein KH, Barch DM, Gold JM, Goldberg TE, Green MF, Heaton RK. Identification of separable cognitive factors in schizophrenia. Schizophr Res. 2004;72:29-39.
17. Turski WA, Nakamura M, Todd WP, Carpenter BK, Whetsell WO Jr, Schwarcz R. Identification and quantification of kynurenic acid in human brain tissue. Brain Res. 1988;454:164-169.
18. Kessler M, Terramani T, Lynch G, Baudry M. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem. 1989;52:1319-1328.
19. Ganong AH, Lanthorn TH, Cotman CW. Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res. 1983;273:170-174.
20. Schwarcz R, Du F, Schmidt W, et al. Kynurenic acid: a potential pathogen in brain disorders. Ann N Y Acad Sci. 1992;648:140-153.
21. Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry. 2001;50:521-530.
22. Erhardt S, Blennow K, Nordin C, Skogh E, Lindström LH, Engberg G. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett. 2001;313:96-98.
23. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases nonalpha7 nicotinic receptor expression: physiopathological implications. J Neurosci. 2001;21:7463-7473.
24. Lozada AF, Wang X, Gounko NV, et al. Glutamatergic synapse formation is promoted by a7-containing nicotinic acetylcholine receptors. J Neurosci. 2012;32:7651-7661.
25. Young JW, Geyer MA. Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia. Biochem Pharmacol. 2013;86:1122-1132.
26. Chess AC, Bucci DJ. Increased concentration of cerebral kynurenic acid alters stimulus processing and conditioned responding. Behav Brain Res. 2006;170:326-332.
27. Chess AC, Landers AM, Bucci DJ. L-kynurenine treatment alters contextual fear conditioning and context discrimination but not cue-specific fear conditioning. Behav Brain Res. 2009;201:325-331.
28. Chess AC, Simoni MK, Alling TE, Bucci DJ. Elevations of endogenous kynurenic acid produce spatial working memory deficits. Schizophr Bull. 2007;33:797-804.
29. Erhardt S, Schwieler L, Emanuelsson C, Geyer M. Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiatry. 2004;56:255-260.
30. Shepard PD, Joy B, Clerkin L, Schwarcz R. Micromolar brain levels of kynurenic acid are associated with a disruption of auditory sensory gating in the rat. Neuropsychopharmacology. 2003;28:1454-1462.
31. Pellicciari R, Rizzo RC, Costantino G, et al. 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. 2006;1:528-531.
32. Erhardt S, Olsson SK, Engberg G. Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders. CNS Drugs. 2009;23:91-101.
33. Okuno E, Nakamura M, Schwarcz R. Two kynurenine aminotransferases in human brain. Brain Res. 1991;542:307-312.
34. Guidetti P, Amori L, Sapko MT, Okuno E, Schwarcz R. Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J Neurochem. 2007;102:103-111.
35. Han Q, Cai T, Tagle DA, Li J. Structure, expression, and function of kynurenine aminotransferases in human and rodent brains. Cell Mol Life Sci. 2010;67:353-368.
36. Amori L, Guidetti P, Pellicciari R, Kajii Y, Schwarcz R. On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J Neurochem. 2009;109:316-325.
37. Guidetti P, Hoffman GE, Melendez-Ferro M, Albuquerque EX, Schwarcz R. Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia. 2007;55:78-92.
38. Wu HQ, Pereira EF, Bruno JP, Pellicciari R, Albuquerque EX, Schwarcz R. The astrocyte-derived alpha7 nicotinic receptor antagonist kynurenic acid controls extracellular glutamate levels in the prefrontal cortex. J Mol Neurosci. 2010;40:204-210.
39. Zmarowski A, Wu HQ, Brooks JM, et al. Astrocyte-derived kynurenic acid modulates basal and evoked cortical acetylcholine release. Eur J Neurosci. 2009;29:529-538.
40. Amori L, Wu HQ, Marinozzi M, Pellicciari R, Guidetti P, Schwarcz R. Specific inhibition of kynurenate synthesis enhances extracellular dopamine levels in the rodent striatum. Neuroscience. 2009;159:196-203.
41. Wu HQ, Okuyama M, Kajii Y, Pocivavsek A, Bruno JP, Schwarcz R. The systemically active kynurenine aminotransferase II inhibitor BFF816 raises extracellular dopamine and glutamate levels in several regions of the rat brain. Soc Neurosci Abstr. 2012;37:771.29.
42. Pocivavsek A, Wu HQ, Potter MC, Elmer GI, Pellicciari R, Schwarcz R. Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology. 2011;36:2357-2367.
43. Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods. 1984;11:47-60.
44. Okuno E, Schmidt W, Parks DA, Nakamura M, Schwarcz R. Measurement of rat brain kynurenine aminotransferase at physiological kynurenine concentrations. J Neurochem. 1991;57:533-540.
45. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci. 2012;13:465-477.
46. Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic a7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proc Natl Acad Sci USA. 2013;110:12078-12083.
47. Sathyasaikumar KV, Stachowski EK, Wonodi I, et al. Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull. 2011;37:1147-1156.
48. Barch DM, Ceaser A. Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci (Regul Ed). 2012;16:27-34.
49. Simpson EH, Kellendonk C, Kandel E. A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron. 2010;65:585-596.
50. Chapin DS, Campbell B, Strick CA, Kozak R. The impact of a KAT II inhibitor on performance in the rat sustained attentional task (SAT) and conditioned avoidance responding (CAR). Soc Neurosci Abstr. 2010;35:472.16.
51. Dounay AB, Anderson M, Bechle BM, et al. PF-04859989 as a template for structure-based drug design: identification of new pyrazole series of irreversible KAT II inhibitors with improved lipophilic efficiency. Bioorg Med Chem Lett. 2013;23:1961-1966.
52. Potter MC, Elmer GI, Bergeron R, et al. Reduction of endogenous kynurenic acid formation enhances extracellular glutamate, hippocampal plasticity, and cognitive behavior. Neuropsychopharmacology. 2010;35:1734-1742.
53. Abbott A, Roberts BM, Turner L, et al. Inhibition of kynurenine aminotransferase II (kat II) protects against ketamine-induced cognitive impairment and improves spatial working memory. Soc Neurosci Abstr. 2010;35:472.18.