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Cellular mechanistic bases for classification of clinically useful anticonvulsant drugs.

Anticonvulsant drug effects on mammalian central neurons in primary cell cultures were investigated. The concentrations at which these drugs limited repetitive firing of action potentials were measured. Their effects on postsynaptic responses to iontophoretically applied GABA were also compared. Based on effects of anticonvulsant drugs on in-vitro assays and action on seizures in man and experimental animals, a classification of clinical anticonvulsants is proposed based on cellular mechanisms of action. Three categories are identified. The mechanisms of action at the cellular level may be useful in predicting clinical efficacy of anticonvulsants under development. The concentration dependence of the in-vitro actions may predict further the therapeutic range of the drug and the mechanisms associated with clinical toxicity.