Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs.
The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.
Ishii
R
R
Research and Development Laboratories, Maruho, Kyoto, Japan.
Furuta
M
M
Hashimoto
M
M
Naruse
T
T
Gallico
L
L
Ceserani
R
R
D000336:Aerosols; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D000996:Antitussive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019343:Citric Acid / Q000008:administration & dosage / Q000009:adverse effects; D003061:Codeine / Q000008:administration & dosage / Q000494:pharmacology; D003371:Cough / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007823:Laryngeal Nerves / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D053778:Thiazolidines
D000336:Aerosols; D000925:Anticoagulants; D000996:Antitussive Agents; D013844:Thiazoles; D053778:Thiazolidines; D019343:Citric Acid; C087933:moguisteine; D003061:Codeine