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Anesth Analg 2006;102:135-140
© 2006 International Anesthesia Research Society
doi: 10.1213/01.ane.0000189102.09347.2e

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{dagger}, and Peter T.-H. Wong, PhD*

Departments of *Pharmacology and {dagger}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.






Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2006 by the International Anesthesia Research Society.