Betotastine besilate

Abstract

The antiallergic activity of betotastine besilate was evaluated in comparison to that of other compounds in various rat models of allergy. Betotastine besilate inhibited histamine release from rat peritoneal mast cells and inhibited LTB 4 and 5-HETE production in peritoneal cells at high concentrations (1 mM). Following oral administration at doses ranging from 0.1-30 mg/kg p.o., betotastine inhibited the homologous passive cutaneous anaphylaxis (PCA) reaction in a dose-dependent fashion (ID 30 = 0.38 mg/kg p.o.), an effect which lasted for more than 8 h. This effect was significant at a dose of 1 mg/kg, and was superior to that of ketotifen, terfenadine, cetirizine and epinastine. No tolerance developed following administration to rats for 8 days (2). The compound also dose-dependently inhibited histamine-induced allergic skin reactions in rats (ID 30 = 0.10 mg/kg), with the effect lasting for more than 4 h postdosing. This effect was significant at doses of 0.1 and 1.0 mg/kg, and was again superior to that of the above reference compounds. Oral betotastine (30 mg/kg) suppressed to decrease in histamine content in pleural cells in a rat model of concanavalin A-induced pleurisy. Taken together, these results indicate that betotastine besilate is a potent and long-acting antiallergic agent whose activity is due to histamine antagonism (2). The antiallergic activity of betotastine was also evaluated in several guinea pig models of bronchoconstriction (2-4). Like the reference compounds ketotifen, terfenadine and cetirizine, betotastine besilate dose-dependently prevented severe asthmatic reactions induced in guinea pigs by histamine inhalation or antigen exposure (ED 50 = 0.01 and 0.3 mg/kg p.o., respectively). The compound also inhibited antigen-induced airway hyperresponsiveness in acutely sensitized guinea pigs at doses of 1 mg/kg p.o. or higher (3).

A Novel Synthetic Method for Bepotastine, a Histamine H1 Receptor Antagonist

“…In conclusion, we have developed an efficient, alternative, and industrially scaleable process for the production of (+)-(S)-4-{4-[(4-chlorophenyl) (2-pyridyl) methoxy]piperidino} butyric acid, bepotastine (1), a histamine H1-receptor antagonist, and its pharmaceutically acceptable salts (bepotastine besilate (4) and bepotastine calcium (5)) from the (S)-3 via diastereomeric crystallization of the racemic compound (3) using N-benzyloxycarbonyl-L-aspartic acid (NCbzLAA).…”