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Cyclooxygenase-1 (COX-1) inhibition by a selective inhibitor valeryl salicylate, or nonselective inhibitors at 10 mg/kg, including aspirin, ibuprofen, indomethacin, and picroxicam, attenuated by 29%-46% the duration of loss of righting reflex induced by diazepam (20 mg/kg) in mice. On the other hand, arachidonic acid (20 mg/kg) increased the duration of diazepam-induced loss of righting reflex by 48%. This effect of arachidonic acid was abolished by aspirin. However, aspirin at 10 mg/kg also did not alter the effects of diazepam (5 mg/kg) on spontaneous activity and rotarod performance. These findings strongly suggest that one or more COX products, most likely prostaglandins, play a significant role in modulating the hypnotic effect of diazepam. Elucidating the mechanism involved may further our understanding of the pharmacology of benzodiazepines.


Xuejing Liu, Tat Leang Lee, Peter T-H Wong. Cyclooxygenase-1 inhibition shortens the duration of diazepam-induced loss of righting reflex in mice. Anesthesia and analgesia. 2006 Jan;102(1):135-40

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PMID: 16368818

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