Inhaled pinacidil, an ATP-sensitive K+ channel opener, and moguisteine have potent antitussive effects in guinea pigs.
We investigated whether inhaled pinacidil and moguisteine inhibit capsaicin-induced coughs in guinea pigs. Inhaled pinacidil (15 - 60 microg/ml), an ATP-sensitive K+ channel opener, and moguisteine (15 - 60 microg/ml) each dose-dependently inhibited the number of capsaicin-induced coughs. The antitussive effects of pinacidil and moguisteine were significantly antagonized by pretreatment with glibenclamide (10 mg/kg, i.p.), an ATP-sensitive K+ channel blocker. However, pretreatment with naloxone methiodide (10 mg/kg, s.c.) had no significant effect on the antitussive effects of either pinacidil or moguisteine. On the other hand, inhaled dihydrocodeine (15 - 60 microg/ml) also dose-dependently suppressed the number of capsaicin-induced coughs. The antitussive effect of inhaled dihydrocodeine was significantly antagonized by pretreatment with naloxone methiodide (10 mg/kg, s.c.), but not by glibenclamide (10 mg/kg, i.p.). These results indicate that inhaled pinacidil and moguisteine both attenuate capsaicin-induced coughs. Pinacidil and moguisteine may exert their antitussive effects through the activation of ATP-sensitive K+ channels in the tracheobronchial tract. Furthermore, it is possible that ATP-sensitive K+ channels may be involved in the antitussive effects of peripherally acting non-narcotic antitussive drugs.
Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Kayo
K
Morita
Kenji
K
Onodera
Junzo
J
Kamei
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D000996:Antitussive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology; D003061:Codeine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D020110:Pinacidil / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D053778:Thiazolidines
D000996:Antitussive Agents; D015221:Potassium Channels; D013844:Thiazoles; D053778:Thiazolidines; D009270:Naloxone; C087933:moguisteine; D020110:Pinacidil; D000255:Adenosine Triphosphate; C014481:dihydrocodeine; D002211:Capsaicin; D005905:Glyburide; D003061:Codeine