Preclinical Pharmacology of Desloratadine, a Selective and Nonsedating Histamine H1 Receptor Antagonist

Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is an active metabolite of loratadine (CAS 79794-75-5) that exhibits qualitatively similar pharmacodynamic activity with a relative oral potency in animals 2.5-4 times greater than loratadine. Its antihistaminic effect lasts 24 h. Desloratadine was shown to be a selective H1 antagonist with more potent antihistaminic activity in vitro than either loratadine or terfenadine (CAS 50679-08-8), as indicated by its displacement of 3H-mepyramine from H1 receptors in rat brain, guinea pig brain, and guinea pig lung, and by its antagonism of histamine-induced contractions of guinea pig ileum. Antihistaminic activity and anitallergic effects also were observed in vivo. After oral administration, desloratadine was 2.5 to 4 times more potent than loratadine in protecting against histamine-induced lethality in the guinea pig and paw edema in the mouse; after topical administration, it was almost 10 times more potent in antagonizing histamine-induced increases in nasal microvascular permeability in the guinea pig. Histamine-induced changes in pulmonary resistance and compliance were also prevented by oral administration of desloratadine and loratadine in the monkey. An oral antiallergic effect was demonstrated by important reductions of acute bronchospasm in the allergic monkey and potent inhibition of allergic cough in the guinea pig. These preclinical studies provide evidence that desloratadine is an antihistaminic agent with a greater potency than loratadine and, together with results from numerous published studies, suggest an antiallergic effect of desloratadine.