[Anticonvulsant activity of sodium valproate and various calcium antagonists during their combined use in mice]

The antiepileptic efficacy of complex of some drugs acting on different epileptic mechanisms was studied in the experiments on mice using the maximal electroshock seizure test. Combined anticonvulsant effects were evaluated by the isobolographic method, various doses of drugs were compared in proportion to their ED50. The results showed that 1,4-dihydropyridines (nifedipine, ryodipine and IOS-1.1212) but not phenylalkylamine (verapamil) and benzothiazepine (diltiazem) possessed anticonvulsant activity. Combined use of 1,4-dihydropyridines--ryodipine and IOS-1.1212--allowed to decrease ED50 of each drug by two times (additive effect), whereas combined use of calcium antagonists of various groups--nifedipine and diltiazem--resulted in the reduction of ED50 by 12 times. The combinations of sodium valproate with dihydropyridines (nifedipine, IOS-1.1212 and ryodipine) produced potentiation effect: ED50 of each drug could be decreased by 3, 3 and 30 times, respectively. The potentiating effect of the drugs under studies suggested to be resulted from the enhancement of inhibitory GABAergic mechanisms (valproate effect) and the suppression of the hyperactivation mechanism of Ca entrance (calcium antagonists effect). These and earlier reported data obtained in the experiments on the models of focal and generalized epilepsy show that complex pathogenetic therapy in form a combination of the antiepileptic drugs acting on the different basic pathogenic mechanisms of epilepsy is reasonable to be used.