[COMPARATIVE STUDY OF THE INFLUENCE OF BENZIMIDAZOLE DERIVATIVE RU-1205, DIAZEPAM, AND SODIUM VALPROATE ON THE SEIZURE THRESHOLD, ANTICONVULSANT TOLERANCE, AND REBOUND EFFECTS.]

We have studied the effects of acute administration of benzimidazole derivative RU-1205 (9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo(1,2-alpha)benzi- midazole), diazepam, and sodium valproate on the threshold for myoclonic and clonic seizures in response to i.v. infusion of pentylenetetrazole (PTZ) in mice. Furthermore, the effects of chronic administrations of RU-1205 and diazepam on the development of anticonvulsant tolerance and rebound phenomena were evaluated. The TID50 values (the dose of anticonvulsant required to increase the PTZ seizure threshold by 50%) of RU-1205, diazepam, and valproate for my- oclonic seizures were 7.9, 120.4, and 1.2 mg/kg (i.p.), respectively. TID50 of RU-1205, diazepam, and valproate for clonic seizures were 7.9, 116.9, and 1.3 mg/kg (i.p.), respectively The chronic administration of RU-1205 (31 mg/kg, i.p., 28 days) did not lead to the development of anticonvulsant tolerance or rebound effect after discontinuation of treatment. The anticonvulsant effect of diazepam (5 mg/kg, i.p., 28 days) in chronically treated mice was gradually abo- lished and the rebound effect was observed after the discontinuation of treatment.