The sedative-hypnotic properties of quazepam, a new hypnotic agent.
7-Chloro-1-(2,2,2-trifluoroethyl)-5-(o-fluorophenyl)-1,3-dihydro-2H-1, 4-benzodiazepine-2-thione (Sch 16134, quazepam) is a new hypnotic drug with demonstrated clinical efficacy. Quazepam has been shown in our laboratories to have potent hypnotic activity and fewer side effects at effective doses than flurazepam, which was studied concurrently. Hypnotic potency was estimated in mice via antagonism of electroshock-induced convulsions (ECS), potentiation of hexobarbital-induced sleeping time, and chlorprothixene potentiation. The respective oral ED50's (95% fiducial limits) in the 3 tests were 0.9 (0.4-2.0), 0.5 (0.3-0.8) and 0.05 (0.02-0.08) mg/kg for quazepam and 1.6 (1.1-2.3), 0.6 (0.4-1.0) and 0.11 (0.07-0.42) mg/kg for flurazepam. The duration of action of quazepam as measured by antagonism of ECS in mice was similar to that of flurazepam at equi-effective doses but quazepam had a faster onset. When potential tolerance to hypnotic efficacy was studied, quazepam did not show tolerance after dosing 20 mg/kg p.o. twice daily (b.i.d.) for 5 days, whereas tolerance was seen with flurazepam at equi-effective doses b.i.d. for 5 days. In conscious, unrestrained squirrel monkeys and cats, quazepam produced sedation with less ataxia and less evidence of CNS stimulant action than flurazepam. On the basis of the aforementioned studies, quazepam should be an effective hypnotic with less potential for ataxia, paradoxical excitation, and tolerance than flurazepam.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D002415:Cats; D002749:Chlorprothixene / Q000494:pharmacology; D004361:Drug Tolerance; D004597:Electroshock; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D006993:Hypnotics and Sedatives; D008297:Male; D051379:Mice; D004856:Postural Balance / Q000187:drug effects; D012453:Saimiri
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D002749:Chlorprothixene; D006591:Hexobarbital; C025130:quazepam