Pharmacological studies of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivatives (450191-S, rilmazafone hydrochloride) (VII). Comparison of sleep-inducing activities between young and elderly rhesus monkeys

Abstract

The sleep-inducing activities of 450191-S (rilmazafone hydrochloride) were compared among two groups of elderly and one group of young rhesus monkeys, and the relationship between blood levels of five active metabolites of 450191-S and sleep-inducing activities was also examined. Oral administration of 450191-S, 1 mg/kg, caused the quick appearance of slow wave deep sleep (SWDS) and its stable continuity in elderly monkeys, and no significant differences in various sleep parameters were observed among the two groups of eight elderly monkeys. An increase of SWDS was always accompanied by a high blood level of active metabolite M-2. On the other hand, in the young rhesus monkey group, the amount of SWDS and its mean continuity were significantly less, and differences were evident in sleep parameters obtained from a nocturnal 14 hr observation. In conclusion, the difference of sleep-inducing activities between elderly and young monkeys seem to be caused by a difference in the blood level of active metabolites of 450191-S, particularly M-2.