COMPARATIVE ACTIONS OF PHENYTOIN AND OTHER ANTICONVULSANT DRUGS ON POTASSIUM-STIMULATED AND VERATRIDINE-STIMULATED CALCIUM-UPTAKE IN SYNAPTOSOMES

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 220  (1) , 29-34
Abstract
The actions of phenytoin and several anticonvulsant drugs on veratridine-stimulated (Na-dependent) and K-stimulated (Na-independent) Ca uptake were studied in isolated nerve terminals (synaptosomes) from rat cerebral cortex. Phenytoin inhibited both veratridine- and K-induced Ca uptake but was more potent against veratridine. Inhibition of veratridine-stimulated Ca uptake by phenytoin appeared to be a competitive relationship, whereas the interaction between K and phenytoin was noncompetitive. Hydroxyphenyl-phenylhydantoin, mephenytoin and ethylphenylhydantoin had actions similar to phenytoin but all were substantially less potent. Carbamazepine, phenobarbital, diazepam and lidocaine also inhibited veratridine- and K-stimulated C uptake, but ethosuximide and valproic acid were ineffective. Only carbamazepine and lidocaine had a relatively selective action against veratridine which was similar to phenytoin, and only these 3 drugs were active at concentrations which approximate their clinically effective anticonvulsant blood levels. Phenytoin apparently inhibited Na and Ca conductances in nervous tissue by separate and probably independent mechanisms. Inhibition of Na uptake (perhaps associated with inhibition of Ca uptake) in nervous tissues was evidently a mechanism of action responsible for some of the selective antiepileptic effects and/or analgesic effects of phenytoin, carbamazepine and idocaine.

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