Abstract
The anti-allergic activity of betotastine besilate (betotastine), a new anti-allergic drug, was investigated in several allergy models of rats in comparison with other anti-allergic drugs. 1) Orally administered betotastine (0.1-30 mg/kg) inhibited homologous passive cutaneous anaphylaxis (PCA) in rats in a dose-dependent manner (ID30-value: 0.38 mg/kg). The inhibitory activity of betotastine was significant at 1 mg/kg and was more potent than that of ketotifen, terfenadine, cetirizine and epinastine. The PCA-inhibitory activity of betotastine lasted more than 8 hr after administration, and the repeated administration of betotastine for 8 days did not induce drug-tolerance. 2) Orally administered betotastine inhibited the histamine-induced skin reaction in rats in a dose-dependent manner (ID30: 0.10 mg/kg), and the inhibitory activity lasted more than 4 hr after the administration. Its inhibitory activity was significant at 0.1 and 1 mg/kg and was more potent than those of ketotifen, terfenadine, cetirizine and epinastine. 3) Betotastine suppressed histamine release from rat peritoneal mast cells at a high concentration (10-3 M). 4) In concanavalin A-induced rat pleurisy, orally administered betotastine (30 mg/kg) suppressed the decrease of histamine content in pleural cells. 5) Betotastine suppressed the leukotoriene B4 and 5-HETE production in rat peritoneal cells at a high concentration (10-3 M). These results suggest that betotastine has a potent and long acting anti-allergic activity, and these effects are mainly due to histamine antagonistic activity.
