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ANESTHETIC PHARMACOLOGY

Cyclooxygenase-1 Inhibition Shortens the Duration of Diazepam-Induced Loss of Righting Reflex in Mice

Xuejing Liu, BSc^*, Tat Leang Lee, MBBS, MMed, FANZCA, and Peter T.-H. Wong, PhD^*

Departments of *Pharmacology and Anesthesia, Faculty of Medicine, National University of Singapore, 18 Medical Drive, Kent Ridge, Singapore

Address correspondence and reprint requests to Peter T.-H. Wong, PhD, Faculty of Medicine, National University of Singapore, 18 Medical Drive, Kent Ridge, Singapore 117597. Address e-mail to phcwth{at}nus.edu.sg.

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.