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September 1976

Anticonvulsant Drug Mechanisms: Phenytoin, Phenobarbital, and Ethosuximide and Calcium Flux in Isolated Presynaptic Endings

Author Affiliations

From the departments of pharmacology and of neurology and neurological surgery, Washington University School of Medicine, St Louis.

Arch Neurol. 1976;33(9):626-629. doi:10.1001/archneur.1976.00500090032006

• Phenytoin, phenobarbital, ethosuximide, and procaine hydrochloride were evaluated for their ability to inhibit Ca flux 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.

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