EVIDENCE FOR PERIPHERAL MECHANISMS MEDIATING THE ANTITUSSIVE ACTIONS OF OPIOIDS IN THE GUINEA-PIG

1. Comparisons were made between the doses required of aerosol and intraperitoneally administered morphine, dextromethorphan, codeine and the specific peripherally acting mu-receptor agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) to suppress citric acid-induced coughing in conscious guinea pigs. 2. Estimated ID50s for inhibition of numbers of coughs induced by an aerosol of 5% citric acid were 1.0 and 2.4 mg/kg for intraperitoneally administered morphine and dextromethorphan, respectively. 3. The estimated ID50s after inhalation of morphine and dextromethorphan as aerosols were almost-equal-to 2.2 and almost-equal-to 12-mu-g/kg, respectively. 4. Aerosilized codeine (almost-equal-to 72-mu-g/kg, n = 5) significantly inhibited coughing by 62 +/- 23% whereas 3 mg/kg, i.p. was required to significantly reduce coughing by a similar degree (60 +/- 6%, n = 7). 5. Inhalation of DALDA (almost-equal-to 7.2-mu-g/kg, n = 7) also significantly inhibited coughing. 6. The antitussive effect of inhaled morphine (almost-equal-to 7.2-mu-g/kg, n =11) was inhibited after administration of 3 mg/kg of either naloxone hydrochloride or naloxone methylbromide intraperitoneally. 7. The results support the hypothesis that effects at a peripheral site can make a major contribution to the antitussive actions of these drugs.