Assessment of antimuscarinic activity of topical and oral antihistamines

Key Points

Fort Lauderdale, FL-The active components of several antihistamine products on the market possess anticholinergic activity in vitro, which suggests that they could have adverse ocular side effects. The results of a review of seven oral and topical compounds, however, indicate that epinastine (Elestat, Inspire Pharmaceuticals) has minimal antimuscarinic effects but high histamine receptor potency, a combination that makes it an attractive option for the treatment of ocular allergies, particularly for patients with a history of dry eye disease, said Kurt Brubaker, clinical research scientist at Inspire Pharmaceuticals, Durham, NC.

He and colleagues at the company, including the senior author of the study, José L. Boyer, PhD, conducted the research. Dr. Boyer is vice president, molecular pharmacology. The findings were presented in a poster at the annual meeting of the Association for Research in Vision and Ophthalmology.

Receptor inhibition

This incubatory step was followed by stimulation with a maximally effective concentration of acetylcholine, and the muscarinic receptor response was measured as increases in intracellular calcium.

The antihistamines used in the experiment were azelastine (Optivar, Meda Pharmaceuticals), cetirizine (Zyrtec, McNeil-PPC), desloratadine (Clarinex, Schering-Plough), fexofenadine (Allegra, Sanofi Aventis), ketotifen fumarate (Zaditor, Novartis), olopatadine (Patanol, Alcon Laboratories), and epinastine.

The primary target of most anti-allergy medications is the H1 histamine receptor, but nonselective properties of those agents, such as antimuscarinic activity, could cause ocular drying or other unwanted side effects, Brubaker said. Ideal characteristics of an anti-allergy medication would be a high affinity for the H1 receptor and low antimuscarinic activity.