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- W2980528070 abstract "Abstract 1-(2-0-Chi orobenzoyl-4-chlorophenyl)-5-glycyl-aminoethyl-3-dimethyl-carbamoyl-1H-1,2,4-triazol hydrochloride, dihydrate (450191-S) is one of the 1H-1,2,4 triazolyl benzophenone derivatives synthesized in our Research Laboratories. 450191-S is a ring-opened benzodiazepine which dissolves 4.0% in water at 25°C. A primary screening test indicated that 450191-S had stronger CNS-suppressing effects than previously studied benzodiazepines. The muscle relaxation effect, disturbance of gait and inhibition of traction with 450191-S were surprisingly weaker than those of control drugs. Furthermore, the anesthetic potentiation effect of 450191-S for chlorprothixen and thiopental-Na was stronger than that of diazepam and was closer to those of nitrazepam. These effects suggested the compound could be used as a sleep-inducer with fewer side effects to somatic functions. Thus, polygraphic analysis of sieep-wakefulness cycles was performed with rhesus monkeys with chronically-indwelling brain electrodes. 450191-S at doses of 0.3, 1.0, 3.0 mg/kg p.o. produced dose-dependent induction of sleep including quick onset of sleep, steady continuity of slow wave sleep without suppression of REM sleep, and less hangover effect the following morning. The effective dose of 450191-S required to induce “sleep” in rhesus monkeys was below 1.0 mg/kg p.o.; 450191-S also caused no disturbance of somatic functions or disturbance of gait which appeared with administration of all other sleep-inducers at usual doses. Fewer adverse side effects including drug-dependence liability were found with 450191-S." @default.
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- W2980528070 date "1983-01-01" @default.
- W2980528070 modified "2023-09-28" @default.
- W2980528070 title "450191-S, a new potent sleep-inducer with little muscle relaxation effect in animals." @default.
- W2980528070 doi "https://doi.org/10.1016/s0021-5198(19)64821-3" @default.
- W2980528070 hasPublicationYear "1983" @default.
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