Anticonvulsant drug actions on GABA responses and sustained repetitive firing of neurons in cell culture

Abstract

We have studied barbiturate, benzodiazepine (BDZ), [beta]-carboline, triazolopyridazine, piperazine carboxylate, hydantoin, iminostilbene, valproate, and succinmide actions on GABA responses and sustained, high frequency repititive firing of mouse neurons in cell culture. Barbiturates, clinically used BDZ, zopiclone and C1 218,872 enhanced GABA responses. Ro 15-1788 and propyl-[beta]-carboline were partial agonists at BDZ receptors while DMCM was an inverse agonist. Phenytoin, carbamazepine, phenobarbital, diazepam and valproic acid limited sustained repetitive firing. We suggest that enhancement of GABAergic inhibition and limitation of sustained high frequency repetitive firing may be anticonvulsant mechanisms of action.