Anticholinergic effects of antihistamine drugs used in the clinic

RATIONALE: Histamine release and stimulation of histamine receptor(s) is one of the primary events in the allergic response and inhibition of histamine receptor activity has been successful in treating allergic diseases. Interaction of antihistamines with other receptors such as muscarinic receptors is the cause of common adverse effects of these drugs. In this study, we examined the antimuscarinic activity of marketed antihistamines including Allegra®(fexofenadine), Clarinex®(desloratadine), Elestat®(epinastine), Optivar®(azelastine), Patanol®(olopatadine), Zaditor®(ketotifen), and Zyrtec®(cetirizine).

METHODS: The ability of antihistamines to interact with muscarinic receptors was evaluated in vitro using cells stably expressing one of the five human muscarinic receptors (M1-M5).

RESULTS: None of the studied drugs had agonist activity on any of the muscarinic receptor cell lines. In contrast, desloratadine and ketotifen were full antagonists at all five muscarinic receptor subtypes with potencies (IC50 values) ranging between 84 and 4938 nM. Little to no antimuscarinic activity was observed for cetirizine, epinastine and fexofenadine. Azelastine was a partial or full antagonist depending on the receptor subtype with IC50 values ranging from 4,697 to 13,955 nM, while olopatadine was a partial antagonist at M1 (IC50 = 4,772 ± 731 nM) and M4 (IC50 = 14,390 ± 2525 nM) receptors.

CONCLUSIONS: This study demonstrates that several marketed antihistamines (Clarinex®, Optivar®, Patanol® and Zaditor®) possess marked anticholinergic activity with potential to cause adverse ocular side effects such as dryness.