Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H-1 receptor antagonist - 2nd communication: Lack of central nervoussystem and cardiovascular effects

dDesloratadine (descarboethoxyloratadine, CAS 100643-71-8) is a selective h istamine H-1 antagonist that exhibits qualitatively similar pharmacodynamic activity to its parent, loratadine (CAS 79794-75-5), but is 2.5-4 times mo re potent orally. In studies of central nervous system (CNS) effects that m ight lead to sedation, desloratadine had no behavioral, neurological or aut onomic effects in the conscious mouse and rat. At large multiples of the an tihistaminic dose in the mouse, it did not inhibit convulsions caused by el ectroconvulsive shock and inhibited acetic acid-induced writhing only at a dose approximately 1,000 times the antihistaminic dose in the mouse. Deslor atadine had no effects on blood pressure, heart rate or electrocardiographi c parameters in the rat or guinea pig or on electrocardiographic parameters in the monkey. Notably, there was no effect on the corrected Q-wave to T-w ave (QTc) interval. Desloratadine did not inhibit IK, channel human ether-a -go-go-related gene (HERG)-induced current in a study in which HERG was exp ressed in Xenopus oocytes. In the rat, desloratadine did not cause effects in urine volume, electrolytes or creatinine, or inhibit gastric emptying or intestinal transit, or cause any harmful effects on gastric mucosa. The re sults of these preclinical studies provide evidence that desloratadine is a safe antihistamine without CNS or cardiovascular effects.