Kynurenines in neurodegenerative disorders: Therapeutic consideration

Advances in Experimental Medicine and Biology

Volumn 541, Issue , 2003, Pages 169-183

  Klivényi, Péter ^a   Toldi, József ^a   Vécsei, László ^a  

^a UNIVERSITY OF SZEGED   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

2 METHOXYBENZOYLALANINE; 3 HYDROXYKYNURENINE; 3,4 DICHLOROBENZOYLALANINE; 3,4 DIMETHOXY N [4 (3 NITROPHENYL)THIAZOL 2 YL]BENZENESULFONAMIDE; 4 CARBOXYMETHYLAMINO 5,7 DICHLORO 2 QUINOLINECARBOXYLIC ACID; 5,7 DICHLORO 1,2,3,4 TETRAHYDRO 4 (3 PHENYLUREIDO) 2 QUINOLINECARBOXYLIC ACID; 7 CHLORO 4 HYDROXY 3 (3 PHENOXYPHENYL) 2 QUINOLONE; 7 CHLORO 4 HYDROXY 3 PHENYL 2(1H) QUINOLINONE; 7 CHLOROKYNURENIC ACID; BETA INTERFERON; ENZYME INHIBITOR; GAVESTINEL; KYNURENIC ACID; KYNURENIC ACID DERIVATIVE; KYNURENINE; KYNURENINE 3 HYDROXYLASE INHIBITOR; KYNURENINE AMINOTRANSFERASE INHIBITOR; PNU 156561; QUINOLINIC ACID; RO 618048; UNCLASSIFIED DRUG;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AMINO ACID METABOLISM; BRAIN ISCHEMIA; CLINICAL TRIAL; CONFERENCE PAPER; DEGENERATIVE DISEASE; ENZYME MECHANISM; HORMONE ACTION; HORMONE DETERMINATION; HORMONE RECEPTOR INTERACTION; HUMAN; HUNTINGTON CHOREA; MULTIPLE SCLEROSIS; NEUROPATHOLOGY; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PARKINSON DISEASE; PRIORITY JOURNAL; SIDE EFFECT;

AIDS DEMENTIA COMPLEX; ANIMALS; CENTRAL NERVOUS SYSTEM DISEASES; DOWN SYNDROME; ENZYME INHIBITORS; HUMANS; ISCHEMIA; KYNURENINE; MULTIPLE SCLEROSIS; NEURODEGENERATIVE DISEASES; PRODRUGS; SCHIZOPHRENIA;

EID: 0347024127     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: None     Document Type: Conference Paper

References (102)

1. Simon RP, Young RS, Stout S, Cheng J: Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia. Neurosci. Lett. 71, 361-364, (1986).
2. Gill R, Foster AC, Woodruff GN: Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in the gerbil. J. Neurosci. 7, 3343-3349, (1987).
3. Faden AI, Demediuk P, Panter SS, Vink R: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244, 798-800, (1989).
4. Choi DW, Koh JY, Peters S: Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J. Neurosci. 8, 185-196, (1988).
5. Muir KW, Lees KR: Clinical experience with excitatory amino acid antagonist drugs. Stroke 26, 503-513, (1995).
6. Fukui S, Schwarcz R, Rapoport SI, Takada Y, Smith QR: Blood-barrier transport of kynurenines: implications for brain synthesis and metabolism. J. Neurochem. 56, 2007-2017, (1991).
7. Lapin IP: Depressor effect of kynurenine and its metabolites in rats. Life Sci. 19, 1479-1484, (1976).
8. Lapin IP: Kynurenines and seizures. Epilepsia 22, 257-265, (1981).
9. Pinelli A, Ossi C, Colombo R, Tofanetti O, Spazzi L: Experimental convulsions in rats induced by intraventricular administration of kynurenine and structurally related compounds. Neuropharmacology 23, 333-337, (1984).
10. Perkins, MN, Stone TW: An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 247, 184-187, (1982).
11. Kessler M, Baudry M, Terramani T, Lynch G: Complex interactions between a glycin binding site and NMDA receptors. Soc. Neurosci. Abst. 13, 760, (1987).
12. Kessler M, Terramani T, Lynch G, Baudry M: A glycin site associated with NMDA receptors: characterisation and identification of new class of antagonists. J. Neurochem. 52:1319-1328, (1989).
13. Birch PJ, Grossman CJ, Hayes AG: Kynurenate and Fg9041 both competetive and non-competetive antagonist actions at excitatory amino acid receptors. Eur. J. Pharmacol. 151, 313-316, (1988).
14. Birch PJ, Grossman CJ, Hayes AG: Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycin receptor. Eur. J. Pharmacol. 154, 85-88, (1988).
15. Stone TW: Neuropharmacology of quinolinic and kynurenic acids. Pharmacol. Rev. 45, 309-379, (1993).
16. Füvesi J, et al: unpublished observations.
17. Moroni F, Russi P, Carla V, Lombardi G: Kynurenic acid is present in the rat brain and its content increases during development and aging processes. Neurosci. Lett. 94, 145-150, (1988).
18. Moroni F, Alesiani N, Galli A, Mori F, Pecorani R, Carla V, Cherici G, Pellicciari R: Thiokynurenates-a new group of antagonists of the glycin modulatory site of the NMDA receptors. Eur. J. Pharmacol. 375, 87-100, (1991).
19. Vécsei L, Beal MF: Intracerebroventricular injection of kynurenic acid, but not kynurenine, induces ataxia and stereotyped behavior in rats. Brain Res. Bull. 25, 623-627, (1990).
20. Vécsei L, Miller J, MacGarvey U, Beal MF: Kynurenine and probenecid inhibit pentylenetetrazol-and NMDLA-induced seizures and increase kynurenic acid concentrations in the brain. Brain Res. Bull. 28, 233-238, (1992).
21. Turski WA, Schwarcz R: On the disposition of intrahippocampally injected kynurenic acid in the rat. Exp. Brain. Res. 71, 563-567, (1998).
22. Dedek J, Baumes R, Tien-Duc N, Gomeni R, Korf J: Turnover of free and conjugated (sulphonyloxy) dihydroxyphenylacetic acid and homovanillic acid in rat striatum. J. Neurochem. 33, 687-695, (1979).
23. Morrison PF, Morishige GM, Beagles KE, Heyes MP: Quinolinic acid is extruded from the brain by a probenecid-sensitive carrier system: a quantitative analysis. J. Neurochem. 72, 2135-2144, (1999).
24. Stone TW: Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. Prog. Neurobiol. 64, 185-218, (2001).
25. Rios C, Santamaria A: Quinolinic acid is a potent lipid peroxidant in rat brain homogenates. Neurochem. Res. 16, 1139-1143, (1991).
26. Guidetti P, Schwarcz R: 3-Hydroxykynurenine potentiates quinolinate but not NMDA toxicity in the rat striatum. Eur. J. Neurosci. 11, 3857-3863, (1999).
27. Tone S, Takikawa O, Habara-Ohkubo A, Kadoya A, Yoshida R, Kido R: Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA. Nucleic Acid. Res. 18, 367, (1990).
28. Dai W, Gupta SL: Regulation of indoleamine 2,3-dioxygenase gene expression in human fibroblasts by interferon-gamma. Upstream control region discriminates between interferon-gamma and interferon-alpha. J. Biol. Chem. 265, 19871-19877, (1990).
29. Hayaishi O, Okamoto H.: Localization and some properties of kynurenine-3-hydroxylase and kynurenine aminotransferase. Am. J. Clin. Nutr. 24, 805-806, (1971).
30. Alberati-Giani D, Buchli R, Malherbe P, Broger C, Lang G, Kohler C, Lahm HW, Cesura AM: solation and expression of a cDNA clone encoding human kynureninase. Eur. J. Biochem. 239, 460-468, (1996).
31. Toma S, Nakamura M, Tone S, Okuno E, Kido R, Breton J, Avanzi N, Cozzi L, Speciale C, Mostardini M, Gatti S, Benatti L: Cloning and recombinant expression of rat and human kynureninase. FEBS. Lett. 408, 5-10, (1997).
32. Okuno E, Nakamura M, Schwarcz R: Two kynurenine aminotransferases in human brain. Brain Res. 542, 307-312, (1991).
33. Guidetti P, Okuno E, Schwarcz R: Characterization of rat brain kynurenine aminotransferases I and II. J. Neurosci. Res. 50, 457-465, (1997).
34. Csillik A, Knyihar E, Okuno E, Krisztin-Peva B, Csillik B, Vécsei L: Effect of 3-nitropropionic acid on kynurenine aminotransferase in the rat brain. Exp. Neurol. 177, 233-241, (2002).
35. Knyihar-Csillik E, Okuno E, Vecsei L: Effects of in vivo sodium azide administration on the immunohistochemical localization of kynurenine aminotransferase in the rat brain. Neuroscience 94, 269-277, (1999).
36. Gal EM, Sherman AD: Synthesis and metabolism of L-kynurenine in rat brain. J. Neurochem. 30, 607-613, (1998).
37. Guidetti P, Eastman CL, Schwarcz R: 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).
38. Heyes MP, Alchim CL, Wiley A, Major EO, Saito K, Markey SP: Human microglia convert L-tryptophan into the neurotoxin quinolinic acid. Biochem. J. 320, 595-597, (1996).
39. Schwarcz R, Ceresoli G, Guidetti P: Kynurenine metabolism in the rat brain in vivo. Effect of acute excitotoxic insults. Adv. Exp. Med. Biol. 398, 211-219, (1996).
40. Guillemin GJ, Kerr SJ, Smythe GA, Smith DG, Kapoor V, Armati PJ, Croitoru J, Brew BJ: Kynurenine pathway metabolism in human astroyctes: a paradox for neuronal protection. J. Neurochem. 78, 842-853, (2001).
41. Lehrmann E, Molinari A, Speciale C, Schwarcz R: Immunohistochemical visualization of newly formed quinolinate in the normal and excitotoxically lesioned rat striatum. Exp. Brain. Res. 141, 389-397, (2001).
42. Heyes MP, Brew BJ, Martin A, Price RW, Salazar AM, Sidtis JJ, Yergey JA, Mourdian MM, Sadler AE, Keilp J, Rubinow D, Markey SP: Quinolinic acid in cerebrospinal fluid and serum in HIV-1 infection: relationhip to clinical and neurologic status. Ann. Neurol. 29, 202-209, (1991).
43. Heyes MP, Saito K, Lackner A, Wiley CA, Achim CL, Markey SP: Sources of the neurotoxin quinolinic acid in the brain of HIV-1 infected patients and retrovirus-infected macaques. FASEB. J. 12, 881-896, (1998).
44. Halperin JJ, Heyes MP: Neuroactive kynurenines in Lyme borreliosis. Neurology 42, 43-50, (1992).
45. Rejdak K, Bartosik-Psujek H, Dobosz B, Kocki T, Grieb P, Giovannoni G, Turski WA, Stelmasiak Z: Decreased level of kynurenic acid in cerebrospinal fluid of relapsing-onset multiple sclerosis patients. Neurosci. Lett. 331, 63-65, (2002).
46. Flanagan EM, Erickson JB, Viveros OH, Chang SY, Reinhard Jr JF: Neurotoxin quinolinic acid is selectively elevated in spinal cords of rats with experimental allergic encephalomyelitis. J. Neurochem. 64, 1192-1196, (1995).
47. Chiarugi A, Cozzi A, Ballerini C, Massacesi L, Moroni F: Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis. Neuroscience 102, 687-95, (2001).
48. Cammer W: Oligodendrocyte killing by quinolinic acid in vitro. Brain Res. 896, 157-160, (2001).
49. Guillemin GJ, Kerr SJ, Pemberton LA, Smith DG, Smythe GA, Armati PJ, Brew BJ: IFN-betalb induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment. J. Interferon. Cytokine. Res. 21, 1097-1101, (2001).
50. Quinolinic acid: an endogenous metabolite that produces axon-sparing lesions in rat brain. Science 219, 316-318, (1983).
51. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB: Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 321, 168-171, (1986).
52. Reynolds GP, Pearson SJ, Halket J, Sandler M: Brain quinolinic acid in Huntington's disease. J. Neurochem. 50, 1959-1960, (1988).
53. Schwarcz R, Tamminga CA, Kurlan R, Shoulson I: CSF levels of quinolinic acid in Huntington's disease and schizophrenia. Ann. Neurol. 24, 580-582, (1988).
54. Heyes MP, Saito K, Crowley JS, Davis LE, Demitrack MA, Der M, Dilling LA, Elia J, Kruesi MJP, Lackner A, Larsen SA, Lee K, Leonard HL, Markey SP, Martin A, Milstein S, Mouradian MM, Pranzatelli MR, Quearry BJ, Salazar A, Smith M, Straus SE, Sunderland T, Swedo SE, Tourtellotte WW: Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurologic disease. Brain 115, 1249-1273, (1992).
55. Guidetti P, Wu HQ, Schwarcz R: In situ produced 7-chlorokynurenate provides protection against quinolinate-and malonate-induced neurotoxicity in the rat striatum. Exp. Neurol. 163, 123-130, (2000).
56. Widner B, Leblhuber F, Fuchs D: Increased neopterin production and tryptophan degradation in advanced Parkinson's disease. J. Neural. Transm. 109, 181-189, (2002).
57. Ogawa T, Matson WR, Beal, MF, Myers RH, Bird ED, Milbury P, Saso S: Kynurenine pathway abnormalities in Parkinson's disease. Neurology 42, 1702-1706, (1992).
58. Heyes MP, Nowak Jr TS: Delayed increases in regional brain quinolinic acid follow transient ischemia in the gerbil. J. Cereb. Blood. Flow. Metab. 10, 660-667, (1990).
59. Saito K, Nowak TS Jr, Markey SP, Heyes MP: Mechanism of delayed increases in kynurenine pathway metabolism in damaged brain regions following transient cerebral ischemia. J. Neurochem. 60, 180-192, (1993).
60. Saito K, Nowak Jr TS, Markey SP, Heyes MP: Delayed increases in kynurenine pathway metabolism in damaged brain regions following transient cerebral ischemia. J. Neurochem. 60, 180-192, (1992).
61. Barattè S, Molinari A, Veneroni O, Speciale C, Benatti L, Salvati P: Temporal and spatial changes of quinolinic acid immunoreactivity in the gerbil hippocampus following transient cerebral ischemia. Mol. Brain. Res. 59, 50-57, (1998).
62. Sinz EH, Kochanek PM, Heyes MP, Wisniewski SR, Bell MJ, Clark RSB, Dekosky ST, Blight AR, Marion DW: Quinolinic acid is increased in CSF and associated with mortality after traumatic brain injury in humans. J. Cereb. Blood. Flow. Metab. 18, 610-615, (1998).
63. Blight AR, Cohen TI, Saito K, Heyes MP: Quinolinic acid accumulation and functional deficits following experimental spinal cord injury. Brain 118, 735-752, (1995).
64. Blight AR, Leroy Jr EC, Heyes MP: Quinolinic acid accumulation in injured spinal cord: time course, distribution, and species differences between rat and guinea pig. J. Neurotrauma. 14, 89-98, (1997).
65. Lapin IP: Stimulant and convulsive effects of kynurenines injected into brain ventricles in mice. J. Neural. Transm. 42, 37-43, (1978).
66. 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. 48, 273-278, (1984).
67. McMaster OG, Du F, French ED, Schwarcz R: Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: evidence for mediation by NMDA receptors. Exp. Neurol. 113, 378-385, (1991).
68. McMaster OG, Baran H, Wu HQ, Du F, French ED, Schwarcz R: Gamma-acetylenic GABA produces axon-sparing neurodegeneration after focal injection into the rat hippocampus. Exp. Neurol. 124, 184-191, (1993).
69. Carpenedo R, Chiarugi A, Russi P, Lombardi G, Carla V, Pellicciari R, Moroni F, Mattoli L: Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. Neuroscience 61, 237-244, (1994).
70. Nakagawa Y, Asai H, Miura T, Kitoh J, Mori H, Nakano K: Increased expression of the 3-hydroxyanthranilate-3,4-dioxygenase gene in brain of epilepsy-prone E1 mice. Mol. Brain. Res. 58, 132-137, (1998).
71. Nakano K, Asai H, Kitoh J: Abnormally high activity of 3-hydroxyanthranilate 3,4-dioxygenase in brain of epilepsy-prone E1 mice. Brain. Res. 572, 1-4, (1992).
72. Nakano K, Takahashi S, Mizobuchi M, Kuroda T, Kitoh KJ: High levels of quinolinic acid in brain of epilepsy-prone E1 mice. Brain. Res. 619, 195-198, (1993).
73. Heyes MP, Wyler AR, Devinsky O, Yergey JA, Markey SP, Nadi NS: Quinolinic acid concentrations in brain and cerebrospinal fluid of patients with intractable complex partial seizures. Epilepsia 31, 172-177, (1990).
74. Yamamoto H, Shindo I, Egawa B, Horiguchi K: Kynurenic acid is decreased in cerebrospinal fluid of patients with infantile spasms. Pediatr. Neurol. 10, 9-12, (1994).
75. Yamamoto H, Murakami H, Horiguchi K, Egawa B: Studies on cerebrospinal fluid kynurenic acid concentrations in epileptic children. Brain. Dev. 17, 327-329, (1995).
76. Schwarcz R, Rassoulpour A, Wu HQ, Medoff D, Tamminga CA, Roberts RC: Increased cortical kynurenate content in schizophrenia. Biol. Psychiatry. 50, 521-530, (2001).
77. Tamminga CA: Schizophrenia and glutamatergic transmission. Crit. Rev. Neurobiol. 12, 21-36, (1998).
78. Baran H, Jellinger K, Derecke L: Kynurenine metabolism in Alzheimer's disease. J. Neural. Transm. 106, 165-181, (1999).
79. Baran H, Cairns N, Lubec B, Lubec G: Increased kynurenic acid levels and decreased brain kynurenine aminotransferase 1 in patients with Down syndrome. Life. Sci. 58, 1891-1899, (1996).
80. Hargreaves RJ, Rigby M, Smith D, Hill RG: Lack of effect of L-687,414 ((+)-cis-4-methyl-HA-966), an NMDA receptor antagonist acting at the glycine site, on cerebral glucose metabolism and cortical neuronal morphology. Br. J. Pharmacol. 110, 36-42, (1993).
81. Baron BM, Harrison BL, Miller FP, McDonald IA, Salituro FG, Schmidt CJ, Sorensen SM, White HS, Palfreyman MG: Activity of 5,7-dichlorokynurenic acid, a potent antagonist at the NMDA receptor-associated glycine binding site. Mol. Pharmacol. 38, 554-561, (1990).
82. Baron BM, Harrison BL, McDonald IA, Meldrum BS, Palfreyman MG, Salituro FG, Siegel BW, Slone AL, Turner JP, White HS: Potent indole- and quinoline-containing NMDA antagonists at the strychnine-insensitive glycine binding site. J. Pharmacol. Exp. Ther. 262, 947-956, (1992).
83. Leeson PD, Carling RW, Moore KW, Moseley AM, Smith JD, Stevenson G, Chan T, Baker R, Foster AC, Grimwood S, Kemp JA, Marshall GR, Hoogsteen K: 4-Amido-2-carboxytetrahydroquinolines. Structure-activity relationships for antagonism at the glycine site of the NMDA receptor. J. Med. Chem. 35, 1954-1968, (1992).
84. Kulagowski JJ, Baker R, Curtis NR, Leeson PD, Mawer IM, Moseley AM, Ridgill MP, Rowley M, Stansfield I, Foster AC: 3′-(Arylmethyl)-and 3′-(aryloxy)-3-phenyl-4-hydroxyquinolin-2(1H)-ones: orally active antagonists of the glycine site on the NMDA receptor. J. Med.Chem. 37, 1402-1405, (1994).
85. Bristow LJ, Flatman KL, Hutson PH, Kulagowski JJ, Leeson PD, Young L, Tricklebank MD: The atypical neuroleptic profile of the glycine/N-methyl-D- aspartate receptor antagonist, L-701324, in rodents. J. Pharmacol. Exp. Therap. 277, 578-585, 1996.
86. Salituro FG, Tomlinson RC, Baron BB, Demeter DA, Weintraub HJR, McDonald IA: Design, synthesis and molecular modeling of 3-acylamino-2-carboxyindole NMDA receptor glycine-site antagonists. Bioorg. Med Chem. Lett. 1, 455-460, (1991).
87. Rao TS, Gray NM, Dappen MS, Cler JA, Mick SJ, Emmett MR, Iyengar S, Monahan JB, Cordi AA, Wood PL: Indole-2-carboxylates, novel antagonists of the NMDA-associated glycine recognition site-in vivo characterization. Neuropharmacology 32, 139-147, (1993).
88. Sacco RL, DeRosa JT, Haley EC Jr, Levin B, Ordronneau P, Phillips SJ, Rundek T, Snipes RG, Thompson JL: The Glycine Antagonist in Neuroprotection Americas Investigators. Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial. JAMA 285, 1719-1728, (2001).
89. Nozaki K, Beal MF: Neuroprotective effects of L-kynurenine on hypoxia-ischemia and NMDA lesions in neonatal rats. J. Cereb. Blood. Flow. Metab. 12, 400-407, (1992).
90. Vécsei L, Beal MF: Influence of kynurenine treatment on open-field activity, elevated plus-maze, avoidance behaviors and seizures in rats. Pharmacol. Biochem. Behav. 37, 71-76, (1992).
91. Wu H-Q, Guidetti P, Goodman JH, Varasi M, Ceresoli-Borroni G, Speciale C, Scharfman HE, Schwarcz R: Kynurenergic manipulations influence excitatory amino acid receptor function and excitotoxic vulnerability in the rat hippocampus in vivo. Neuroscience 97, 243-251, (2000).
92. Hokari M, Wu H-Q, Schwarcz R, Smith QR: Facilitated brain uptake of 4-chlorokynurenine and conversion to 7-chlorokynurenic acid. Neuroreport 8, 15-18, (1996).
93. Wu H-Q, Salituro FG, Schwarcz R: 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).
94. Wu H-Q, Lee S-C, Scharfman HE, Schwarcz R: L-4-chlorokynurenine attenuates kainate-induced seizures and lesions in the rat. Exp. Neurol. 177, 222-232, (2002).
95. Battaglia G, La Russa M, Bruno V, Arenare L, Ippolito R, Copani A, Bonina F, Nicoletti F: Systemically administered D-glucose conjugates of 7-chlorokynurenic acid are centrally available and exert anticonvulsant activity in rodents. Brain. Res. 860, 149-156, (2000).
96. Röver S, Cesura AM, Hugenin P, Kettler R, Szente A: Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl) benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J. Med. Chem. 40, 4378-4385, (1997).
97. Russi P, Alesiani M, Lombardi G, Davolio P, Pellicciari R, Moroni F: Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. J. Neurochem. 59, 2076-2080, (1992).
98. Chiarugi A, Moroni F: Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)alanine (mNBA) and 3,4-dimethoxy-[N-4-(3- nitrophenyl)thiazol-2-yl]benzenesulfonamide (Ro 61-8048), two potent and selective inhibitors of kynurenine hydroxylase. Neuropharmacology 38, 1225-1233, (1999).
99. Cozzi A, Carpenedo R, Moroni F: Kynurenine hydroxylase inhibitors reduce ischaemic brain damage. Studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[N-4-(nitrophenyl)thiazol-2-yl]benzenesulfonamide (Ro61-8048) in models of focal or global brain ischaemia. J. Cereb. Blood. Flow. Metab. 19, 771-777, (1999).
100. Urenjak J, Obrenovitch TP: Kynurenine 3-hydroxylase inhibition in rats: effects on extracellular kynurenic acid concentration and N-methyl-D-aspartate- induced depolarisation in the striatum. J. Neurochem. 75, 2427-2433, (2000).
101. Todd WP, Carpenter BK, Schwarcz R: Preparation of 4-halo-3- hydroxyanthranilates and demonstration of their inhibition of 3-hydroxanthranilate oxygenase in rat and human brain tissue. Prep. Biochem. 19, 155-165, (1989).
102. Walsh JL, Todd WP, Carpenter BK, Schwarcz R: 4-Halo-3-hydroxyanthanilic acids: potent competitive inhibitors of 3-hydroxyanthranilic acid oxygenase in vitro. Biochem. Pharmacol. 42, 985-990, (1991).