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The experiments on 286 mice of two lines (SHR and C57BL/6) showed that 3-indoipyruvate, a natural keto analogue of tryptophan and a precursor of serotonin and kynurenic acid) possesses the selective dose-dependent (100-500 mg/kg, intraperitoneally) protective effect against quinolinate-induced convulsions. At prolonged administration (50-100 mg/kg for 10 days twice a day) its efficiency drastically increased. It is supposed that the mechanism of the anticonvulsant action of 3-indolpyruvate involves an enhancement of synthesis of kynurenic acid, a blocker of N-methyl-D-aspartate receptors, and at chronic administration--also an increase of sensitivity and density of these receptors.

All excitatory amino acid antagonists studied: diethyl esters of aspartic (DEEA) and glutamic (DEEG) acids, 2-amino-3-phosphono-propionic acid (APPA) and 2-amino-4-phosphono-butanoic acid (APBA), diminished the amplitude of excitatory postsynaptic potentials (EPP) of the locust (Locusta migratoria migratorioides) muscle fibers and arbitrary blocked glutamate (GLU) and aspartate (ASP) responses. Kynurenine (KYN) and quinolinic (QUI) acid had no effect on EPP even at a concentration of 2 X 10(-2) M. The antagonists were not strictly selective against intracerebroventricularly administered endogenous convulsants: GLU, ASP, KYN and QUI and in simulation of experimental seizures in mice. The antagonists structurally similar to ASP prevented ASP- and KYN-induced seizures in lower doses than GLU derivatives. Anti-KYN, but not anti-QUI DEEA, DEEG, APPA and APBA efficacy suggests that KYN and QUI act on different structures or binding sites.

Benzobarbital, primidone, phenobarbital, phynytoin and trimethadionum (in order of decreasing activity) were moderately effective against DL-kynurenine (50 micrograms, i. c. v.)-induced seizures in SHR albino male mice. Diazepam was ineffective even in doses of 15 and 25 mg/kg. Against seizures induced by quinolinic acid (5 micrograms, i. c. v.) anticonvulsants, particularly primidone and phenytoin, were more effective than against kynurenine-induced seizures. Diazepam was slightly effective in high doses of 7-15 mg/kg. Primidone and benzobarbital in doses used (10-50 mg/kg) were ineffective against strychnine and pentylenetetrazol. Selective efficacy of primidone and benzobarbital in this model of seizures suggests that kynurenine and quinolinic acid could be involved in the grand mal fits in epileptic patients.

Phenibut, sodium hydroxybutyrate and baclofen are selectively effective against seizures induced in mice by the endogenous metabolites of tryptophan, L-kynurenine and quinolinic acid. The seizures were not affected by the drugs in doses under study. Depakine and aminooxyacetic acid as well as diazepam and phenobarbital appeared the most effective against pentylenetetrazole seizures. GABA and muscimol administered intracerebroventricularly merely prolonged the latency of seizures. Dissimilarities in the GABA-ergic mechanisms of the anticonvulsant effects of the drugs under consideration are discussed.

Derivatives of GABA which are ineffective against seizures produced by typical convulsants (strychnine, pentylenetetrazole, etc.), phenibut and sodium hydroxybutyrate in doses of 200 mg/kg and higher possess marked anticonvulsant action against seizures induced by intraventricular injection of L-kynurenine and quinolinic acid in mice. Phepiron, a cyclic form of phenibut, had dissimilar action on the effects of L-kynurenine and a quinolinic acid, enhancing that produced by the former agent and diminishing tonic extension and lethality after the latter one. GABA and piracetam appeared to be ineffective. Efficacy of GABA derivatives against seizures produced by L-kynurenine and quinolinic acid suggests that the system of GABA plays a significant role in the genesis of seizures produced by kynurenines.

Selective antagonists of quinolinic acid (2,3-pyridine dicarboxylic acid, QUIN)--an endogenous convulsant tryptophan metabolite, administered intracerebroventricular to mice, were identified during comparison with the following intracerebroventricular convulsants: l-kynurenine, aspartic, glutamic, N-methyl-DL-aspartic and kainic acids. It is suggested that the antagonism arises due to a common fragment of the structure which consists of two carboxylic groups at two nearest carbon atoms of the ring and of one nitrogen atom in the alpha-position. The selective action of the compounds found against QUIN supports the suggestion that QUIN produces seizures via N-methyl-D-aspartate binding sites.