Does naloxone induce relaxation of guinea-pig airway smooth muscle?

The effects of the opiate receptor antagonist naloxone were investigated on isolated preparations of guinea-pig trachealis contracted with either histamine, methacholine or KCl. The commercially available solution of naloxone (Narcan) induced concentration-dependent relaxation of the contracted airway preparations. In stark contrast, aqueous solutions of naloxone were without any significant relaxant effect. Aqueous solutions of the preservatives (methyl and propyl hydroxybenzoate) present in the vehicle used in the commercial formulation of naloxone mimicked exactly the relaxant effects induced by Narcan. Thus, naloxone does not directly induce relaxation of airway smooth muscle. The effects of Narcan can be solely attributed to the activity of the preservatives present in the vehicles. The mechanism underlying the bronchodilator activity of methyl and propyl hydroxybenzoate is unknown but is not related to receptor blockade or to alterations in the intracellular levels of cyclic AMP.