Antimuscarinic effects of antihistamines: quantitative evaluation by receptor-binding assay.
Quantitative evaluation of antimuscarinic effects of antihistamines (H1- and H2-receptor antagonists) was carried out using a receptor-binding assay. The -inhibition constants (Ki values) of twenty seven H1-receptor antagonists, one related antidepressant and three H2-receptor antagonists at H1-receptors and muscarinic receptors in the bovine cerebral cortex were determined. All the H2-receptor antagonists examined showed very low affinity for the muscarinic receptors. On the other hand, some H1-receptor antagonists (mequitazine, cyproheptazine, clemastine, diphenylpyraline, promethazine, homochlorcyclizine and alimemazine) had high affinity for the muscarinic receptors (Ki = 5.0-38 nM). Another group of H1-receptor antagonists (mepyramine, terfenadine, metapyrilen, azelastine, hydroxyzine and meclizine) had low affinity for the muscarinic receptors (Ki = 3,600-30,000 nM). Thus, a broad range of antimuscarinic potencies among the antihistamines was demonstrated. These results should provide helpful information with regard to the clinical and experimental use of antihistamines.
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism; D002417:Cattle; D002540:Cerebral Cortex / Q000187:drug effects; D006633:Histamine Antagonists / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010276:Parasympatholytics; D011738:Pyrilamine / Q000378:metabolism; D011813:Quinuclidinyl Benzilate; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000187:drug effects*
D000928:Antidepressive Agents; D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; D011813:Quinuclidinyl Benzilate; D011738:Pyrilamine