title: Tofizopam enhances the action of diazepam against tremor and convulsions.
abstract: Tofizopam, an anxiolytic 3,4-benzodiazepine, increases the affinity of benzodiazepine receptors for 1,4-benzodiazepines. In this study we investigated whether this increased affinity of the receptors alters the sensitivity of mice to tremor and to convulsions. Convulsions induced by harmane were not affected by tofizopam (50-300 mg/kg), but diazepam (15 mg/kg) increased the ED50 of harmane from 9.9 to 25.1 mg/kg. Tofizopam did not alter the threshold for electroshock-induced convulsions, while a dose of 10 mg/kg diazepam protected mice from convulsions. Low doses of tofizopam (12.5-25 mg/kg) sensitized mice to the tremorogenic effect of harmaline. Diazepam inhibited tremor: the ED50 of harmaline increased by 153% after 50 mg/kg of diazepam. In contrast to 1,4-benzodiazepines, tofizopam has no anticonvulsive effect. It sensitises mice to the tremor induced by harmaline. In combination with diazepam, however, tofizopam enhanced the anticonvulsive and antitremorogenic actions of this 1,4-benzodiazepine by 12-65%. This effect probably results from a tofizopam-induced increase in the occupation of benzodiazepine receptors.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D004597:Electroshock; D006247:Harmine / Q000031:analogs & derivatives; D008297:Male; D051379:Mice; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D014202:Tremor / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D006247:Harmine; C005010:harman; D003975:Diazepam; C012582:tofisopam