ANTITUSSIVE EFFECTS OF 2 SPECIFIC KAPPA-OPIOID AGONISTS, U-50,488H AND U-62,066E, IN RATS

The effects of highly selective agonists of κ-opioid receptors, namely, U-50, 488H and U-62,066E, on the capsaicin-induced cough reflex in rats were studied. Intracisternal (i.cist.) injection of U-50, 488H and of U-62,066E significantly decreased the number of coughs in a dose-dependent manner. The antitussive potency of i. cist. injection of these two κ-opioid agonist was similar to that of morphine. Intraperitoneal (i.p.) injection of U-50, 488H and of U-62, 066E also decrease the number of coughs, again in a dose-dependent manner. The antitussive effects of U-50, 488H and U-62, 066E were blocked by norbinatorphimine, an antagonsit of κ-opoiod receptors. Methysergide, administered i. cist. (3 nmol), antagonized the antitussive effects of U-50, 488H and U-62, 066E. However, ketanserin had no effect on the ntitussive effects of these κ-opioid agonists. These data suggest that U-50, 488H and U-62, 066E exert their antitussive effect on rats through stimulation of κ-opioid receptors. Furthermore, with respect to the antitussive effects of κ-opioid agonists, the system that involves 5-HT1 receptors may be more important than the system that involves 5-HT2 receptors. © 1990.