7-Chlorokynurenic acid antagonizes the anticonvulsant activity of D-cycloserine in maximal electroshock seizures.
This study evaluated the anticonvulsant activity of D-cycloserine against maximal electroshock seizures in rats. Systematically administered D-cycloserine (i.p.) inhibited maximal electroshock-induced tonic hindlimb extension in a dose-dependent manner with an ED50 of 153 mg/kg. No neurological deficit was detected at any dose of D-cycloserine. In contrast, L-cycloserine had no effect on the maximal electroshock seizures. Administration of the strychnine-insensitive glycine receptor antagonist 7-chlorokynurenic acid (100 nmol, i.c.v.) significantly antagonized the anticonvulsant activity induced by D-cycloserine. Centrally administered D-cycloserine (i.c.v.) induced significant anticonvulsant activity 1-2 h after administration with an approximate ED50 of 5 mumol. 7-Chlorokynurenic acid (100 nmol, i.c.v.) significantly antagonized the anticonvulsant activity of centrally administered D-cycloserine. L-Cycloserine (i.c.v., 2 h) induced no significant anticonvulsant activity. These results provide evidence that the anticonvulsant activity of D-cycloserine in maximal electroshock seizures may be mediated by strychnine-insensitive glycine receptors.
Peterson
S L
SL
Department of Medical Pharmacology and Toxicology, Texas A&M University, College Station 77843-1114.
D000818:Animals; D000927:Anticonvulsants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003523:Cycloserine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000927:Anticonvulsants; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid