suvorexant and brotizolam

We previously reported that brotizolam, but not suvorexant, delayed recovery from isoflurane anesthesia in mice. However, the effects of hypnotics may be altered by the circadian rhythm. Locomotor activity was measured using sighted (ICR and C57BL/6J) and blind (FVB/N and C3H/HeN) mice, and the effects of hypnotics on isoflurane anesthesia were compared during the light and dark periods. In sighted mice, recovery induced by brotizolam was delayed in the light period, while that by suvorexant was delayed in the dark period. In C57BL/6J mice, delayed recovery induced by brotizolam was marked, and that by suvorexant was observed in the light and dark periods. Locomotor activity was low in the last 6 h of the dark period in blind mice, and was similar to that in the light period. In blind mice, delayed recovery induced by brotizolam was identical in both periods, while suvorexant did not influence recovery from isoflurane anesthesia. These results suggest that the effects of hypnotics on isoflurane anesthesia are altered by the circadian rhythm and that daily light-dark stimuli may be required for the chronopharmacological effects of hypnotics.

Topics: Anesthesia Recovery Period; Anesthesia, Inhalation; Anesthetics, Inhalation; Animals; Azepines; Chronopharmacokinetics; Circadian Rhythm; GABAergic Neurons; Hypnotics and Sedatives; Isoflurane; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred ICR; Motor Activity; Photoperiod; Time Factors; Triazoles

We investigated the effects of sleep-inducing agents with different mechanisms of action on the loss of the righting reflex induced by isoflurane or a mixture of medetomidine, midazolam, and butorphanol (MMB), followed by atipamezole reversal. Chlorpromazine and brotizolam delayed recovery from both types of anesthesia, whereas the melatonin receptor agonist ramelteon had no effect. The orexin receptor antagonist suvorexant delayed recovery from anesthesia only in the case of MMB, while the sleep-promoting supplement glycine only delayed recovery in the case of isoflurane. These results suggest that the simple comparison method is applicable for testing substances expected to exert sleep-inducing effects.

Topics: Anesthesia; Anesthetics; Animals; Azepines; Butorphanol; Chlorpromazine; Drug Combinations; Imidazoles; Indenes; Isoflurane; Male; Medetomidine; Mice; Mice, Inbred ICR; Midazolam; Orexin Receptor Antagonists; Sleep Aids, Pharmaceutical; Triazoles