title: Evidence for peripheral mechanisms mediating the antitussive actions of opioids in the guinea pig.
abstract: 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 approximately 2.2 and approximately 12 micrograms/kg, respectively. 4. Aerosilized codeine (approximately 72 micrograms/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 (approximately 7.2 micrograms/kg, n = 7) also significantly inhibited coughing. 6. The antitussive effect of inhaled morphine (approximately 7.2 micrograms/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.
authors.affiliation: Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
authors.forename: J K
authors.initials: JK
authors.lastname: Callaway
authors.forename: R G
authors.initials: RG
authors.lastname: King
authors.forename: A L
authors.initials: AL
authors.lastname: Boura
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002951:Citrates; D019343:Citric Acid; D003061:Codeine / Q000008:administration & dosage / Q000494:pharmacology; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D003915:Dextromethorphan / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007274:Injections, Intraperitoneal; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology; D010111:Oxymorphone / Q000494:pharmacology; D010525:Peripheral Nerves / Q000187:drug effects*
chemical_list: D000996:Antitussive Agents; D002951:Citrates; D009294:Narcotics; D009842:Oligopeptides; C063076:tyrosyl-arginyl-phenylalanyl-lysinamide; D019343:Citric Acid; D009270:Naloxone; D003915:Dextromethorphan; D009020:Morphine; D010111:Oxymorphone; D003061:Codeine