Comparative anticholinergic activities of 10 histamine H1 receptor antagonists in two functional models

We determined the relative rank orders of anticholinergic potencies of 10 antihistamines in two functional bioassays: (1) an in vitro assay measuring inhibition of carbachol-induced contractions of isolated guinea pig trachealis muscle, (2) an in vivo bioassay comparing systemic hypotensive responses to bolus i.v. injections of acetylcholine before and after infusions of an antihistamine in anaesthetized rats. In vitro, the rank order of anticholinergic potencies of the antihistamines was cyproheptadine>promethazine>desloratadine>diphenhydramine>loratadine>chlorpheniramine>hydroxyzine>pyrilamine. The pA2 values ranged from 8.2±0.4 for cyproheptadine to 4.8±0.4 for pyrilamine. Fexofenadine and cetirizine (up to 3×10−4 M) were inactive. In vivo, five antihistamines showed anticholinergic activity: cyproheptadine>promethazine>desloratadine>loratadine>diphenhydramine. The remaining antihistamines had no significant effect at i.v. infusion doses up to 50 ìmol/kg. Cetirizine and fexofenadine did not antagonize cholinergic responses in either model.