[Pharmacological studies of a new sleep-inducer, 1H-1,2,4-triazolyl benzophenone derivative (450191-S) (V). General pharmacological activities].
General pharmacological activities of 450191-S were studied in various species of animals and compared with those of reference benzodiazepines (BDZ). 450191-S at doses of 10 mg/kg slightly decreased (-5 degrees C) the rectal temperature of rabbits. 450191-S decreased respiratory and heart rates in anesthetized cats, but the effects were less than those of diazepam or triazolam. 450191-S increased respiratory and heart rates in conscious dogs, but had no effect on the blood pressure, electrocardiogram and autonomic nervous system in cats and dogs. The drug displayed a slight spasmolytic activity in the small intestine of guinea pigs and a slight inhibitory effect on isolated non-pregnant and pregnant uteri of rats. These effects were less than those of diazepam or nitrazepam. Below doses of 25 mg/kg, 450191-S did not affect urinary volume and electrolyte excretions in rats. It also decreased brain norepinephrine (NE) turnover rates in rats, but decreased NE and dopamine turnover rates in mice. These effects of 450191-S were less than those of nitrazepam. 450191-S was found to be minimally irritating to the ocular mucosa in rabbits and did not irritate the stomach and small intestine in rats. These effects were also compared with those of active metabolites of 450191-S, M-1, M-2, M-A, M-3 and M-4, and the superiority of the mother compound over its metabolites was clarified.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D001569:Benzodiazepines; D001679:Biogenic Amines / Q000032:analysis; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002415:Cats; D002490:Central Nervous System / Q000187:drug effects; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012119:Respiration / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001679:Biogenic Amines; D006993:Hypnotics and Sedatives; D014230:Triazoles; D001569:Benzodiazepines; C041075:rilmazafone