MOGUISTEINE - A NOVEL PERIPHERAL NONNARCOTIC ANTITUSSIVE DRUG

1 The antitussive effects of moguisteine have been compared with codeine in several experimental models of cough in guinea-pigs and dogs. 2 Moguisteine and codeine dose-dependently (respective ED(50) values are given in parentheses) inhibited cough induced in guinea-pigs by 7.5% citric acid aerosol (25.2 and 29.2 mg kg(-1), p.o.), by 30 mu M capsaicin aerosol (19.3 and 15.2 mg kg(-1), p.o.), by mechanical stimulation (22.9 and 26.4 mg kg(-1), p.o.) and by tracheal electrical stimulation (12.5 and 13.9 mg kg(-1), p.o.). 3 Moguisteine was effective against cough induced by tracheal electrical stimulation in dogs (ED(50) 17.2 mg kg(-1), p.o.); codeine was not tested because of its emetic effect. 4 After repeated dosing (12-15 days), moguisteine did not induce tolerance in either guinea-pigs or dogs. 5 Moguisteine did not interact with opiate receptors, since it did not show affinity for [H-3]-naloxone binding sites and furthermore naloxone (5 mg kg(-1), s.c.) did not antagonize its antitussive effects. 6 Moguisteine had no antitussive effect after i.c.v. administration (20 mu g), whilst codeine (2-10 mu g) and dextromethorphan (2.5-20 mu g) were highly effective. 7 Our findings demonstrate that moguisteine is a novel peripherally acting non-narcotic antitussive agent, the mode of action of which remains to be elucidated fully.