Ebastine in the light of CONGA recommendations for the development of third-generation antihistamines

Abstract

S Rico1,2, RM Antonijoan1,3, MJ Barbanoj1,2,31Centre d’lnvestigació de Medicaments, Institut de Recerca; Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain; 3Centro de investigación Biomédica en Red de Salud Mental CIBERSAM, SpainAbstract: In 2003 a consensus group on new-generation antihistamines (CONGA) defined the characteristics required for a third-generation H1 antihistamine as there had been much controversy about this issue since the early 1990s. One of the antihistamines that had been claimed to belong to such a group is the second-generation antihistamine, ebastine. The objective of this review is to analyze the pharmacology of ebastine, in light of the CONGA recommendations for the development of new-generation antihistamines: (1) anti-inflammatory properties, (2) potency, efficacy and effectiveness, (3) lack of cardiotoxicity, (4) lack of drug interactions, (5) lack of CNS effects, and (6) pharmacological approach. Ebastine seems to have anti-inflammatory properties that help to ameliorate nasal congestion, though this has not yet been conclusively demonstrated. Its pharmacological–therapeutic profile does not differ greatly from that of other second-generation antihistamines. Its cardiac safety has been widely assessed and no cardiac toxicity has been found at therapeutic doses despite initial concerns. The risk of potentially relevant drug interactions has been investigated and ruled out. Ebastine does not produce sedation at therapeutic doses and drug interaction studies with classical CNS depressants have not demonstrated a synergistic effect. Pharmacologically, ebastine is an H1 inverse agonist. Perhaps the answer to the quest for new-generation antihistamines lies not only in H1 but in a combined approach with other histamine receptors.Keywords: ebastine, antihistamines, third-generation, CONGA, allergy