The antitussive activity of delta-opioid receptor stimulation in guinea pigs

In this study, the activity of the delta-opioid receptor subtype-selective agonist, SB 227122, was investigated in a guinea pig model of citric acid-i nduced cough. Parenteral administration of selective agonists of the delta- opioid receptor (SB 227122), mu-opioid receptor (codeine and hydrocodone), and kappa-opioid receptor (BRL 52974) produced dose-related inhibition of c itric acid-induced cough with ED50 values of 7.3, 5.2, 5.1, and 5.3 mg/kg, respectively. The nonselective opioid receptor antagonist, naloxone (3 mg/k g, i.m.), attenuated the antitussive effects of codeine or SB 227122, indic ating that the antitussive activity of both compounds is opioid receptor-me diated. The delta-receptor antagonist, SB 244525 (10 mg/kg, i.p.), inhibite d the anti-tussive effect of SB 227122 (20 mg/kg, i.p.). In contrast, combi ned pretreatment with beta-funaltrexamine ( mu-receptor antagonist; 20 mg/k g, s.c.) and norbinaltorphimine (kappa-receptor antagonist; 20 mg/kg, s.c.) , at doses that inhibited the antitussive activity of m-and kappa-receptor agonists, respectively, was without effect on the antitussive response of S B 227122 (20 mg/kg, i.p.). The sigma-receptor antagonist rimcazole (3 mg/kg , i.p.) inhibited the antitussive effect of dextromethorphan (30 mg/kg, i.p .), a sigma-receptor agonist, but not that of SB 227122. These studies prov ide compelling evidence that the antitussive effects of SB 227122 in this g uinea pig cough model are mediated by agonist activity at the delta-opioid receptor.