Effects of the calcium channel blocker, verapamil, on asthmatic airway responses to muscarinic, histaminergic, and allergenic stimuli.
The effect of calcium channel blocking agents on bronchomotor tone and airway responsiveness to inhaled provocative stimuli remains controversial. In this study we examined the effects of verapamil (a papaverine derivative) on baseline airway function as well as the response to methacholine, histamine, and ragweed allergen. Verapamil was chosen because of its aqueous solubility and hence suitability for aerosol administration in higher doses than previously given. The effects of 5 mg and 12.5 mg aerosolized verapamil doses were compared with placebo as separate parts of the same study in subjects with ragweed-allergic asthma. Neither dose of verapamil was found to produce bronchodilatation within 30 min after aerosol administration. At the 12.5 mg dose, however, we observed mild to moderate bronchospasm occurring within 5 min of administration, with a return toward baseline within 30 to 40 min. This bronchoconstrictor effect was unrelated to the low osmolarity of the drug solution (33 mosmol/L). Responses to methacholine, histamine, and ragweed allergen were unaltered by drug pretreatment at the 5-mg dose. At the 12.5-mg dose, however, we found significant inhibition of methacholine responsiveness but no effect on histamine or allergen responses. From these studies we conclude that verapamil can influence airway function by modulating agonist-induced bronchoconstriction. The selectivity of this inhibitory effect on muscarinic responses alone, however, leaves questionable the importance of this activity with regard to its clinical implications.
D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D005541:Forced Expiratory Volume; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D014700:Verapamil / Q000627:therapeutic use*
D000485:Allergens; D002121:Calcium Channel Blockers; D008688:Methacholine Compounds; D016210:Methacholine Chloride; D006632:Histamine; D014700:Verapamil