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The non‐cardiac systemic side‐effects of antihistamines: ebastine
Author(s) -
Roberts D. J.,
Gispert J.
Publication year - 1999
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1999.0290s3151.x
Subject(s) - histamine , pharmacology , histamine h1 receptor , in vivo , pilocarpine , medicine , chemistry , anesthesia , receptor , antagonist , biology , microbiology and biotechnology , psychiatry , epilepsy
Ebastine and its active metabolite carebastine show potent antagonism of histamine H 1 ‐mediated phenomena in a wide variety of in vitro and in vivo non‐clinical experimental models. By contrast, activity is not seen against histamine H 2 ‐ or H 3 ‐mediated, nor acetylcholine‐ or serotonin‐mediated phenomena, and both compounds are virtually without effect in models measuring pharmacological effects on the central nervous system (CNS). Explanation of these observations is found in their high selectivity for the histamine H 1 receptor and in their low in vivo potency in displacing [ 3 H]‐mepyramine from central histamine H 1 receptors, indicating that they do not readily pass the blood–brain barrier. These findings have been mirrored in clinical experimental models where oral doses of ebastine (1–30 mg) showed clear dose‐related inhibition of intradermal histamine‐induced weal and flare responses, whereas doses of 90 mg were without anticholinergic effects on salivary flow, cardiovascular reflexes or pilocarpine‐induced miosis. Furthermore, in an extensive series of controlled studies in specific clinical models for measuring objective effects on the CNS, ebastine in single doses of 10–90 mg and repeated doses of 10–30 mg once daily, had no clinically relevant effects on cognitive performance and visual co‐ordination tests, nor on simulated car‐tracking tests and real car‐driving tests. Nor was their any interaction with ethanol or diazepam. On subjective test parameters (questionnaires and visual analogue scales) there were only a few isolated and random incidences of minor increases in some indices of sedation at the highest doses. Not suprisingly, therefore, the clear therapeutic benefit seen during the extensive and international use of ebastine (5–20 mg once daily) in the treatment of seasonal and perennial rhinitis and chronic idiopathic urticaria, has not been accompanied by signs of drug‐induced anticholinergic effects (dry mouth, disturbances of visual accommodation) or sedation, making it an effective and well‐tolerated first‐line treatment alternative to other second‐generation antihistamines.