| Histamines H1 receptor antagonists exhibit varying degrees of anticholinergic activity at muscarinic receptors. This study compared the anticholinergic activity of ten different H1 antagonists in an in vitro functional model of cholinergic antagonism. Antagonist-induced rightward shifts of concentration-response curves to carbachol in guinea-pig isolated tracheal ring segments were assessed. Schild plot analysis and pA 2 calculations were used to compare the potency of each antihistamine. The rank order of potency in vitro was cyproheptadine > promethazine > desloratadine (DCL) > diphenhydramine > loratadine > chlorpheniramine > hydroxyzine > pyrilamine. Fexofenadine and cetirizine did not antagonize carbachol-induced contractions at concentrations up to 0.1 mM. This rank of potencies correlates with the published binding affinities of these drugs at muscarinic receptors. The receptors mediating cholinergic contraction were examined with the muscarinic sub-type specific antagonists pirenzepine, methoctramine, and 4-DAMP. The pA2 values and binding affinities of these antagonists are consistent with the muscarinic M3 receptor mediating contraction. Some first generation and newer generation H1 antagonists inhibit cholinergic contraction, while others do not. Clearly, members of this drug class should be viewed individually. |
