Yasuda S U, Yasuda R P
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Pharmacotherapy. 1999 Apr;19(4):447-51. doi: 10.1592/phco.19.6.447.31041.
Anticholinergic effects are presumed to be the mechanism for the efficacy of chlorpheniramine in symptomatic relief of the common cold. Terfenadine, a second-generation antihistamine, reportedly lacks anticholinergic side effects. We evaluated affinities of two commonly used over-the-counter antihistamines, brompheniramine and chlorpheniramine, as well as terfenadine in comparison with atropine at the five human muscarinic cholinergic receptor subtypes using CHO cells stably transfected with the individual subtypes. Atropine was more potent than all three drugs at m1-m5 (p<0.01). No significant difference was observed between chlorpheniramine and brompheniramine. Atropine, brompheniramine, and chlorpheniramine could not discriminate between m1-m5. Terfenadine demonstrated subtype selectivity at m3. In vitro comparisons in human muscarinic receptor subtypes could potentially be used to predict clinical anticholinergic effects of antihistamines and to target receptor-specific effects of such agents.
抗胆碱能作用被认为是氯苯那敏缓解普通感冒症状的作用机制。据报道，第二代抗组胺药特非那定缺乏抗胆碱能副作用。我们使用稳定转染了各亚型的CHO细胞，评估了两种常用的非处方抗组胺药溴苯那敏和氯苯那敏以及特非那定与阿托品相比，在五种人毒蕈碱胆碱能受体亚型上的亲和力。在m1 - m5受体亚型上，阿托品比所有三种药物的效力更强（p<0.01）。氯苯那敏和溴苯那敏之间未观察到显著差异。阿托品、溴苯那敏和氯苯那敏无法区分m1 - m5受体亚型。特非那定在m3受体亚型上表现出亚型选择性。在人毒蕈碱受体亚型上进行体外比较，可能有助于预测抗组胺药的临床抗胆碱能作用，并针对此类药物的受体特异性作用。
