Involvement of ATP-sensitive K(+) channels in the anti-tussive effect of moguisteine.
The effect of glibenclamide, an ATP-sensitive K(+) channel blocker, on the anti-tussive effect of moguisteine and of pinacidil, an ATP-sensitive K(+) channel opener in guinea pigs was studied. Pinacidil (1 and 5 mg/kg, subcutaneous (s.c.)) dose-dependently reduced the number of coughs. The anti-tussive effect of pinacidil was significantly and dose-dependently antagonized by pre-treatment with glibenclamide (3 and 10 mg/kg, i.p.). Moguisteine (1 and 5 mg/kg, s.c.) dose-dependently reduced the number of coughs. The anti-tussive effect of moguisteine was also reduced by pre-treatment with glibenclamide, in a dose-dependent manner. However, pre-treatment with glibenclamide had no effect on the anti-tussive effects of dihydrocodeine and dextromethorphan. Glibenclamide (10 mg/kg, i.p.), by itself, had no significant effect on the number of coughs. These results suggest that pinacidil and moguisteine may exert their anti-tussive effects through the activation of ATP-sensitive K(+) channels. Furthermore, it is possible that ATP-sensitive K(+) channels may be involved in the anti-tussive effect of peripherally acting non-narcotic anti-tussive drugs.
Morita
K
K
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, Japan.
Kamei
J
J
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D054086:KATP Channels; D008297:Male; D020110:Pinacidil / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines
D018528:ATP-Binding Cassette Transporters; D000996:Antitussive Agents; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D013844:Thiazoles; D053778:Thiazolidines; C092520:uK-ATP-1 potassium channel; C087933:moguisteine; D020110:Pinacidil; D005905:Glyburide