Antitussive effect of K+ channel openers.
The effect of the K(ATP) channel openers, pinacidil and cromakalim, on coughing was studied in guinea pigs exposed to a nebulized aqueous solution of citric acid (0.50 M). Both pinacidil and cromakalim, subcutaneously administered 45 min before the test, inhibited coughing. The D50 (95% CI) were 0.95 +/- 0.90 mg/kg for cromakalim and 3.25 +/- 0.92 mg/kg for pinacidil. Under our experimental conditions, the D50 (95% CI) of codeine was 1.74 +/- 0.75 mg/kg. The combination of cromakalim and pinacidil with codeine produced an additive effect. An additive effect was also produced by the combination of pinacidil with the selective tachykinin NK2 receptor antagonist MEN 10,627 = [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2beta-5beta)]. The antitussive effect of pinacidil and cromakalim was not a consequence of a bronchodilating effect, which was absent at these dose levels under our experimental conditions. These results indicate that K(ATP) channel openers have an opioid-like antitussive effect and may suggest a novel approach to the symptomatic treatment of coughing.
Poggioli
R
R
Department of Biomedical Sciences, University of Modena and Reggio nell'Emilia, Italy.
Benelli
A
A
Arletti
R
R
Cavazzuti
E
E
Bertolini
A
A
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology*; D019343:Citric Acid; D003061:Codeine / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D008297:Male; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000819:agonists*; D015320:Tachykinins / Q000494:pharmacology
D000996:Antitussive Agents; D001993:Bronchodilator Agents; D015221:Potassium Channels; D015320:Tachykinins; D019806:Cromakalim; D019343:Citric Acid; D020110:Pinacidil; D003061:Codeine