European journal of pharmacology
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Comparative Study
Antitussive effect of NS-398, a selective cyclooxygenase-2 inhibitor, in guinea pigs.
Several reports have demonstrated that the number of capsaicin-induced coughs is increased in the presence of prostaglandins in the airway. Moreover, it has been reported that the expression of cyclooxygenase-2, which converts arachidonic acid to prostaglandins, was found in cultured human airway epithelial cells in the absence of inflammatory cytokine stimulation. Thus, it is possible that cyclooxygenase-2 inhibitor may produce an antitussive effect. ⋯ Furthermore, it is possible that the antitussive action of NS-398 does not depend on centrally acting mechanisms, since 5-HT receptors play an important role in the cough-depressant activities of centrally acting antitussive drugs. NS-398 may exert peripheral antitussive effects by inhibiting the release of substance P from capsaicin-sensitive afferent C-fibers in the airways. These results suggest that cyclooxygenase-2 inhibitors may have a therapeutic benefit in reducing coughs.
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Comparative Study
The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice.
Alpha(2)-adrenoceptor agonists potentiate opioid analgesia and alleviate opioid withdrawal. The effects of two alpha(2)-adrenoceptor agonists, clonidine (2 mg/kg) and dexmedetomidine (20 and 100 microg/kg), and the alpha(1)-adrenoceptor antagonist prazosin (0.5 mg/kg) were tested on morphine analgesia, tolerance, and withdrawal in wild-type and alpha(2A)-adrenoceptor knock-out (KO) mice. Analgesia and tolerance were assessed with the tail-flick test. ⋯ Alpha(2A)-Adrenoceptor KO mice exhibited 70% fewer naloxone-precipitated jumps than wild-type mice; weight loss was similar in both genotypes. The alpha(2)-adrenoceptor agonists reduced opioid withdrawal signs only in wild-type mice. We conclude that alpha(2A)-adrenoceptors are not directly involved in morphine analgesia and tolerance, and not critical for potentiation of morphine analgesia by prazosin, but that alpha(2A)-adrenoceptors modulate the expression of opioid withdrawal signs in mice.