Facilitation of diazepam action by anticonvulsant agents against picrotoxin induced convulsions

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Abstract
A subeffective dose (2 mg/kg) of diazepam produced only 50% protection against picrotoxin-induced (PTX) convulsions in rats. Simultaneous administration of GABA and other GABA-ergic substances such as piracetam and sidium valproate, which did not have any effect by themselves, potentiated diazepam action. The onset of convulsions and mortality due to PTX were significantly delayed. The other conventional anticonvulsants phenobarbitone, phenytoin and ethosuximide also enhanced the protective effect of diazepam. Inosine, a putative benzodiazepine ligand, also enhanced diazepam action. These observations are explained on the basis of data from in vitro studies indicating that GABA-ergic agents and barbiturates enhance both the number of benzodiazepine binding sites and benzodiazepine binding. The protective effect of clonidine, however, may be mediated by a different mechanism unrelated to the GABA-ergic system.