Movchan O. Patterns of mechanisms formation of the tolerance to the anticonvulsant drugs

It was established that the development of tolerance to the phenobarbital, carbamazepine, valproate sodium and topiramate effects was observed in the chemoconvulsant models of seizures (corazol, thiosemicarbazide). This phenomenon develops at 7-14-day administration of anticonvulsant drugs. Tolerance to phenobarbital and carbamazepine effects in the model of electrically induced seizures is recorded after 21-day administration of drugs, to lamotrigine - on the 14th day of administration. The possibility of cross-tolerance between phenobarbital, carbamazepine, valproate sodium and topiramate was also observed in the chemoconvulsant models of seizure events. No cross-tolerance between phenobarbital, carbamazepine and lamotrigine was observed in the model of electrically induced seizures. The obtained results suggest that it is not reasonable to increase the anticonvulsant doses to overcome tolerance since such approach may lead to the enhancement of their toxic action without the expected increase of pharmacotherapeutic effect.