Moguisteine: a novel peripheral non-narcotic 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 ED50 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 microM 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 (ED50 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 [3H]-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 micrograms), whilst codeine (2-10 micrograms) and dextromethorphan (2.5-20 micrograms) 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.
Gallico
L
L
Boehringer Mannheim Italia, Research Center, Monza.
Borghi
A
A
Dalla Rosa
C
C
Ceserani
R
R
Tognella
S
S
D000336:Aerosols; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002211:Capsaicin / Q000008:administration & dosage; D002951:Citrates / Q000008:administration & dosage; D019343:Citric Acid; D003061:Codeine / Q000494:pharmacology; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000493:pharmacokinetics; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D053778:Thiazolidines
D000336:Aerosols; D000996:Antitussive Agents; D002951:Citrates; D013844:Thiazoles; D053778:Thiazolidines; D019343:Citric Acid; D009270:Naloxone; C087933:moguisteine; D002211:Capsaicin; D003061:Codeine