Anticonvulsant drug mechanisms. Phenytoin, phenobarbital, and ethosuximide and calcium flux in isolated presynaptic endings.
Phenytoin, phenobarbital, ethosuximide, and procaine hydrochloride were evaluated for their ability to inhibit Ca2+ 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.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005013:Ethosuximide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*; D011343:Procaine / Q000008:administration & dosage / Q000494:pharmacology; D011817:Rabbits; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D011343:Procaine; D005013:Ethosuximide; D010672:Phenytoin; D002118:Calcium; D010634:Phenobarbital