Purchase this article with an account.
Annabelle C. Gallois-Bernos, Robin L. Thurmond; Pharmacology Of Alcaftadine, A New Antihistamine For Ocular Allergy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6426.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Current therapy for ocular allergy includes H1 antihistamines, mast cell stabilizers, dual action antihistamines (H1 antihistamines + mast cell stabilizers), and steroids. Each of these compounds is effective at treating some, or most symptoms of ocular allergy, but none provide a comprehensive therapy. In this report, we describe a combined in vivo and in vitro characterization of alcaftadine, a new antihistamine that exhibits a distinct spectrum of therapeutic properties.
The in vivo assessment of alcaftadine efficacy employed a guinea pig model of conjunctivitis. We compared alcaftadine with ketotifen or dexamethasone for its ability to prevent responses to either instilled histamine or instilled allergen. We then examined the selective binding properties of alcaftadine for three histamine receptor isoforms (H1, H2, and H4) expressed in cultured cell lines. As an additional test of alcaftadine action at H4 receptors, we used a cell-based reporter system to measure function antagonism of histamine action.
Alcaftadine prevented immediate allergic responses with an efficacy comparable to ketotifen, and was also able to attenuate delayed eosinophil influx with potency similar to dexamethasone. Binding studies demonstrated that alcaftadine is high affinity ligand for the H1 receptor with a Ki (3.1 nM) that is comparable to other H1 antihistamines. It also shows a ~ 19 fold higher affinity for the H2 receptor than ketotifen (Ki 58 nM vs. 1.09 µM). In H4 receptor studies, alcaftadine binding displayed a modest affinity, but was also approximately ~ 17 fold higher than values reported for ketotifen (Ki of 2.9 µM vs.50 µM). Using a cellular assay of H4 receptor activity, alcaftadine was also shown to act as an antagonist of H4 receptor signaling.
Overall, the studies suggest that alcaftadine is a histamine H1 receptor antagonist with additional, broad spectrum antihistamine activity and a unique combination of therapeutic efficacies. As such it appears to represent a new class of potential therapies for treatment of allergic conditions.
This PDF is available to Subscribers Only