Diazepam potentiation by glycine in pentylenetetrazol seizures is antagonized by 7-chlorokynurenic acid.
This study evaluated a possible mechanism by which glycine potentiates the activity of diazepam (DZP) and valproic acid (VAL) against the clonic seizures induced by pentylenetetrazol (PTZ) in rats. Neither 7-chlorokynurenic acid (7-CLKYNA) nor strychnine in doses of 10, 50, or 100 nmol ICV significantly altered the clonic seizure response to PTZ. However, 7-CLKYNA (100 nmol, ICV), but not strychnine (100 nmol, ICV), antagonized the anticonvulsant activity induced by coadministration of DZP (1.0 mg/kg, IP) and glycine (40 mmol/kg, PO). Neither 7-CLKYNA (100 nmol, ICV) nor strychnine (100 nmol, ICV) significantly altered the anticonvulsant activity induced by coadministration of VAL and glycine. 7-CLKYNA (100 nmol, ICV) had no effect on the anticonvulsant activity of DZP or VAL in the absence of glycine. These results provide evidence that the glycine potentiation of the anticonvulsant activity of DZP in clonic seizures induced by PTZ may be mediated by the strychnine-insensitive glycine receptor.
Peterson
S L
SL
Department of Medical Pharmacology and Toxicology, Texas A&M University Health Science Center, College Station 77843-1114.
D000818:Animals; D003975:Diazepam / Q000494:pharmacology*; D004357:Drug Synergism; D005998:Glycine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007276:Injections, Intraventricular; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013331:Strychnine / Q000008:administration & dosage / Q000494:pharmacology
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D007736:Kynurenic Acid; D013331:Strychnine; D003975:Diazepam; C057013:7-chlorokynurenic acid; D005998:Glycine; D010433:Pentylenetetrazole