Cellular bases of barbiturate and phenytoin anticonvulsant drug action.

Although anticonvulsant drugs are the mainstay of therapy for epilepsy, their mechanisms of action remain uncertain for several reasons. First, most anticonvulsant compounds have been shown to have multiple physiological, biochemical, and pharmacological actions. It has been difficult, therefore, to determine which specific drug actions produce clinical effects. Second, investigation has often been performed on isolated peripheral or invertebrate neuronal or muscle preparations or on neurons in the intact vertebrate central nervous system. In the former case, the number of drug actions that can be studied is limited, since the pharmacology of these cells is quite unlike that found in the vertebrate central nervous system. In the latter case, the preparation is technically difficult to study and, therefore, limited experimental control is possible. Third, investigators have identified single actions of anticonvulsants and suggested a role in anticonvulsant action without determining if the drug effect is produced at concentrations achieved in the central nervous system during clinical use. Finally, anticonvulsants are often studied at concentrations achieved in serum during clinical use. However, for anticonvulsants that are protein bound, it is important to use therapeutic free-serum concentrations, since Michigun