title: The protective effect of inhaled chlorpheniramine and atropine on bronchoconstriction stimulated by airway cooling.
abstract: We examined the role of histamine release and reflex bronchoconstriction in the bronchoconstriction stimulated by airway cooling. In 8 asthmatic subjects, dose-response curves were determined to isocapnic hyperventilation of cold air 30 min after inhalation of chlorpheniramine maleate (18 mg nebulized during tidal breathing), 2 doses of atropine sulphate (3 mg and 18 mg nebulized), or placebo. Treatments were given on separate days, in random order and under double-blind conditions. The bronchial antihistamine and anticholinergic actions of chlorpheniramine were determined by the effect on histamine and methacholine dose-response curves on another 4 days. Chlorpheniramine was selective as an antagonist against histamine; it increased the mean provocation concentration of histamine to reduce the FEV1 by 20% (PC20) 14.2-fold but increased the mean PC20 methacholine only 1.85-fold. Atropine in the 3-mg dose, previously shown to increase the PC20 methacholine at least 100-fold, had no effect on heart rate or saliva output in contrast to 18 mg, which significantly reduced saliva output and increased heart rate. Chlorpheniramine caused no bronchodilation and a small 1.28-fold increase in the amount of respiratory heat exchange needed to reduce the FEV1 by 10% (PD10RHE). Atropine caused maximal bronchodilation after 3 mg and a dose-dependent increase in PD10RHE (1.16-fold increase after 3 mg and 1.32-fold increase after 18 mg atropine). The effect of chlorpheniramine and atropine 18 mg on PD10RHE was not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects*; D001985:Bronchial Provocation Tests; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D003080:Cold Temperature; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006339:Heart Rate; D006632:Histamine; D006801:Humans; D008297:Male; D008688:Methacholine Compounds; D010812:Physical Stimulation; D012463:Saliva / Q000378:metabolism
chemical_list: D008688:Methacholine Compounds; D002744:Chlorpheniramine; D001285:Atropine; D006632:Histamine