Cyclooxygenase-1 inhibition shortens the duration of diazepam-induced loss of righting reflex in mice.
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.
Liu
Xuejing
X
Department of Pharmacology, Faculty of Medicine, National University of Singapore, 18 Medical Drive, Kent Ridge, Singapore.
Lee
Tat Leang
TL
Wong
Peter T-H
PT
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D003975:Diazepam