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.