| Abstrakt: |
Ebastine (CAS 90729-43-4), cetirizine (CAS 83881-51-0) and loratadine (CAS(79794-75-5) are second generation H[SUB1]-antihistamines of proven efficacy for treating allergy. Recent clinical studies have found ebastine to be more effective than cetirizine or loratadine in alleviating the symptoms of seasonal allergic rhinitis. The objective of this study was to compare the efficacy of these compounds in three guinea-pig models of bronchocon-striction, elicited either by histamine, allergen or leukotriene C[SUB4] (in order to shed) light onto the mechanisms that might explain differences found in clinical studies. In the present experiments, ebastine and cetirizine were equipotent against aerosol histamine-induced bronchospasm in guinea pigs (ED[SUB50] 115 and 100 μg/kg p.o., respectively), while loratadine was three-fold less potent. In the same model the effects of ebastine, loratadine and cetirizine lasted 21, 19 and 15 h, respectively. Ebastine (ED[SUB50] (334)μg/kg p.o.) was the most potent compound in inhibiting allergen-induced bronchospasm in conscious guinea pigs. In vitro studies in tracheally perfused guinea pig lungs demonstrated that ebastine and loratadine inhibited with equal potency the broncho-constriction induced by leukotriene C[SUB4] whilst cetirizine was significantly less potent. Finally, in another in vivo study, ebastine reverted the changes in pulmonary resistance induced by leukotriene C[SUB4] (in anaesthetised guinea pigs, whereas) cetirizine and loratadine were devoid of activity in this model. In accordance with the clinical data, ebastine proved to be the substance with the widest range of application in animal experiments, too. [ABSTRACT FROM AUTHOR] |
