These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


PUBMED FOR HANDHELDS

Search MEDLINE/PubMed


  • Title: Antitussive effect of NS-398, a selective cyclooxygenase-2 inhibitor, in guinea pigs.
    Author: Kamei J, Matsunawa Y, Saitoh A.
    Journal: Eur J Pharmacol; 2004 Aug 23; 497(2):233-9. PubMed ID: 15306209.
    Abstract:
    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. To test this hypothesis, we investigated the effects of N-[2-(cyclohexyloxy)-4-nitrofenyl]-methane sulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl-pyrazole (SC-560), a selective cyclooxygenase-1 inhibitor, on capsaicin-induced coughs in guinea pigs. NS-398 (1-10 mg/kg, p.o.) dose-dependently and significantly reduced the number of capsaicin-induced coughs. In contrast, SC-560 (10 mg/kg, p.o.) did not reduce the number of capsaicin-induced coughs. The antitussive effect of NS-398 (10 mg/kg, p.o.) was not antagonized by pretreatment with methysergide (3 mg/kg, i.p.), a non-selective serotonin (5-HT) receptor antagonist, or glibenclamide (10 mg/kg, i.p.), an ATP-sensitive K(+) channel blocker. Furthermore, although NS-398 did not significantly affect the cough reflex induced by substance P (10(-16) M), it significantly reduced the capsaicin-induced release of substance P in bronchoalveolar lavage fluid (BALF). The present findings clearly show that cyclooxygenase-2 inhibitor, but not cyclooxygenasez-1 inhibitor, has a potent 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.
    [Abstract] [Full Text] [Related] [New Search]