The behavioral effects of
450191-S and its metabolites were investigated in mice, rats, cats and rhesus monkeys, and they were compared with those of related
benzodiazepines (BDZ) such as
diazepam and
nitrazepam.
Oral administration of
450191-S consistently caused sedation without excitability in mice and rats, and it was only 1/2 to 1/266 as potent as the BDZ in producing motor
incoordination as assessed by
traction, rotarod performance and inclined screen tests in mice, induced much less
ataxia in cats and monkeys, and inhibited respiration in anesthetized cats. The locomotor activities of mice and rats measured by Animex and the open field test were not affected by
450191-S, but rearing and preening decreased with
450191-S as with the BDZ.
450191-S was equipotent with
nitrazepam and 2 to 6 times more potent than
diazepam and
estazolam in potentiating
chlorprothixene-induced
hypnosis and
thiopental-Na-induced
anesthesia. These effects were not different with successive 14-day administration of
450191-S. Anti-
pentylenetetrazol,
picrotoxin and
bicuculline convulsions of
450191-S had the same potency as
nitrazepam, but caused much less anti-electroshock convulsion than the BDZ.
450191-S had potent antianxiety activity as observed by anti-aggressive and anti-conflict activities and had almost the same effect as
diazepam on operant behavior. The metabolites M-1, M-2, M-A and M-3 showed approximately the same potency as
450191-S in inducing
anesthetic potentiation and antianxiety activity, but they were much more potent in causing disturbance of the somatic functions. These results indicate that
450191-S possesses inhibitory effects on the central nervous system, including a potent sleep-inducing effect, and is characterized by markedly weak muscle relaxant activity and motor
incoordination.