Affinities of brompheniramine, chlorpheniramine, and terfenadine at the five human muscarinic cholinergic receptor subtypes.
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.
Yasuda
S U
SU
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007, USA.
Yasuda
R P
RP
D000818:Animals; D001285:Atropine / Q000378:metabolism / Q000494:pharmacology; D001977:Brompheniramine / Q000378:metabolism / Q000494:pharmacology; D016466:CHO Cells / Q000378:metabolism; D002744:Chlorpheniramine / Q000378:metabolism / Q000494:pharmacology; D006224:Cricetinae; D006634:Histamine H1 Antagonists / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D011976:Receptors, Muscarinic / Q000145:classification* / Q000378:metabolism*; D013379:Substrate Specificity; D016593:Terfenadine / Q000008:administration & dosage / Q000378:metabolism; D014162:Transfection
D006634:Histamine H1 Antagonists; D011976:Receptors, Muscarinic; D002744:Chlorpheniramine; D016593:Terfenadine; D001285:Atropine; D001977:Brompheniramine