Effects of glycopyrrolate on capsaicin-induced cough in normal volunteers treated with captopril.
The effects of inhibition of angiotensin converting enzyme (ACE) and glycopyrrolate on cough caused by inhaled capsaicin were investigated in a double-blind, randomised cross-over study in twelve normal volunteers. The capsaicin challenge was performed before and 2 h after dosing with 75 mg captopril or matched placebo given orally, and 20, 40 and 60 min after giving 1 mg glycopyrrolate i.v. to each subject. Captopril and placebo did not alter the cough response when compared to baseline. Glycopyrrolate, however, caused a significant increase in the threshold sensitivity (D2) from baseline, and a significant decrease in the total cough response at 40 and 60 min both after captopril and placebo. The D2-baseline and D2-40 min after glycopyrrolate (mean SD), respectively, were 3.2 (1.0); 17.9 (4.2) after placebo and 2.5 (8.5); 23.6 (6.9) after captopril. Elimination of vagal influences implies attenuation of the effects of tachykinins but not those prostaglandins. We postulate that tachykinins, such as substance P, play a more important role than prostaglandins in capsaicin-induced cough. We conclude that the vagus is important in the capsaicin-induced cough reflex, but, as suppression of this reflex by glycopyrrolate was delayed, the relevant receptors are either poorly accessible peripheral receptors or they are located in the central nervous system.
Department of Pharmacology, Faculty of Medicine, University of Pretoria, South Africa.
M
M
van Wyk
D K
DK
Sommers
J R
JR
Snyman
D000280:Administration, Inhalation; D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage; D002216:Captopril / Q000494:pharmacology*; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D006024:Glycopyrrolate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D008297:Male
D002216:Captopril; D002211:Capsaicin; D006024:Glycopyrrolate