Preclinical pharmacology of desloratadine, a selective and nonsedating histamine H1 receptor antagonist. 2nd communication: lack of central nervous system and cardiovascular effects.
Desloratadine (descarboethoxyloratadine, CAS 100643-71-8) is a selective histamine H1 antagonist that exhibits qualitatively similar pharmacodynamic activity to its parent, loratadine (CAS 79794-75-5), but is 2.5-4 times more potent orally. In studies of central nervous system (CNS) effects that might lead to sedation, desloratadine had no behavioral, neurological or autonomic effects in the conscious mouse and rat. At large multiples of the antihistaminic dose in the mouse, it did not inhibit convulsions caused by electroconvulsive shock and inhibited acetic acid-induced writhing only at a dose approximately 1,000 times the antihistaminic dose in the mouse. Desloratadine had no effects on blood pressure, heart rate or electrocardiographic 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-wave (QTc) interval. Desloratadine did not inhibit IKr channel human ether-a-go-go-related gene (HERG)-induced current in a study in which HERG was expressed 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 results of these preclinical studies provide evidence that desloratadine is a safe antihistamine without CNS or cardiovascular effects.
Kreutner
W
W
Schering-Plough Research Institute, Kenilworth, New Jersey, USA.
Hey
J A
JA
Chiu
P
P
Barnett
A
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D002490:Central Nervous System / Q000187:drug effects*; D004064:Digestive System / Q000187:drug effects; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D051381:Rats
D000927:Anticonvulsants; D006634:Histamine H1 Antagonists; D017336:Loratadine; C121345:desloratadine