Effect of sodium valproate, phenobarbital and diazepam during their combined use on convulsions induced by electroshock in mice
Abstract
Complex pathogenetic therapy (CPT) of epilepsy in the form of combined action of drugs enhancing GABA-mediated inhibition was carried out. The anticonvulsant potency of drugs and of their combinations was determined by a maximal electroshock seizure test in mice. Combined anticonvulsant effects were evaluated by the isobolographic method, various doses of drugs were compared in proportion to their ED 50. It was shown that synergistic effects of potentiation type were in all cases of combined use of drugs. ED 50 of each drug could be decreased in combinations of sodium valproate with diazepam by 7 times, phenobarbital with sodium valproate--by 12 times, phenobarbital with diazepam--by 14 times and sodium valproate with phenobarbital and diazepam--by 26 times. Thus, these results suggest that complex use of drugs acting on different mechanisms of GABA-mediated inhibitory control lead to a marked potentiation of the end effect. The obtained data allow to conclude that CPT of epilepsy which can provide potentiation of effects of each drug and a significant reduction of their doses is reasonable to be used.
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