Anticonvulsant Drug Mechanisms

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Abstract
• Phenytoin, phenobarbital, ethosuximide, and procaine hydrochloride were evaluated for their ability to inhibit Caflux into isolated presynaptic endings (synaptosomes) prepared from rabbit neocortex. Calcium influx produced by depolarizing concentrations (69 mM) of K+was inhibited 7% to 63% by phenytoin, phenobarbital, or procaine, whereas ethosuximide was ineffective. Decreased Ca2+influx was observed with as little as 0.08 mM phenytoin and 0.04 mM phenobarbital. In contrast, 4 mM procaine was needed to produce an effect. These results lead to the conclusion that ability to produce membrane stabilization is not a property of all anticonvulsant drugs; however, this property may be essential for the action of drugs effective in the treatment of major seizures.