THE EFFECT OF 443C81, A MU-OPIOID RECEPTOR AGONIST, ON THE RESPONSE TO INHALED CAPSAICIN IN HEALTHY-VOLUNTEERS

Activation of mu-opioid receptors on sensory nerves in the lung represents an attractive mechanism for reducing cough and reflex bronchoconstriction. We have examined the effect of the peptide 443C81, a peripherally acting mu-opioid agonist, on the cough and reflex increase in respiratory resistance (R(rs)) produced by capsaicin in nine healthy male volunteers. Using a randomised, double-blind crossover design, each subject inhaled either saline, 1 mg ml-1 443C81 or 4 mg ml-1 443C81 for 10 min from an ultrasonic nebuliser. The cough response to a range of doses of inhaled capsaicin and the increase in R(rs) caused by inhalation of a single subtussive dose of capsaicin were measured before and after each treatment. There was no evidence of an effect of either 1 or 4 mg ml-1 443C81 on cough or increase in R(rs) produced by capsaicin when compared with the saline placebo. It is concluded that inhalation of this mu-opioid receptor agonist had no effect on capsaicin-induced cough or reflex bronchoconstriction in healthy volunteers.