EFFECTS OF METERGOLINE OR PISOTIFEN ON CAPSAICIN-INDUCED COUGH IN NORMAL VOLUNTEERS TREATED WITH BUSPIRONE

Serotonin (5-hydroxytryptamine [5-HT]) has been shown to act as a modu lator of the cough reflex in some species; however, the subtype of the 5-HT receptor influencing the cough reflex remains to be clarified. i n this study, we compared the influence of prolonged treatment with bu spirone (a 5-HT1A dualist), alone or combined with metergorline (a 5-H T1 antagonist), pisotifen (a 5-HT2 antagonist), or placebo, on capsaic in-induced cough. Fourteen normal volunteers with no history of respir atory infection within the preceding 6 weeks were involved in the stud y. For the construction of capsaicin cough dose-response curves the su bjects took single breaths at 30-second intervals of either sodium chl oride or a range of doses of capsaicin (0.4-50 nmol) in random order h orn a nebulizer controlled by a breath-activated dosimeter, The number of coughs occurring in the 30 seconds following each inhalation was n oted and the results were expressed as the total cough count, the conc entration of capsaicin causing two coughs (D2), and the concentration causing five or more coughs (D5). There were no statistically signific ant differences in D2, D5, or the total cough court with any of the tr eatment regimens when compared with the baseline capsaicin response ob tained on the first study day. This study, therefore, shows that buspi rone does not significantly influence capsaicin-induced cough in human s, either done or in the presence of various 5-HT antagonists. However , the buspirone/pisotifen combination tended to be more cough-suppress ing.