Antihistamines in late-phase clinical development for allergic disease
Abstract
Allergic rhinitis (AR) is a global health concern and shares a high comorbidity with asthma. Recent research suggests that different allergic diseases, such as AR, asthma, allergic conjunctivitis and chronic idiopathic urticaria (CIU), are evoked by common pathological mechanisms characterised by the release of histamine and other inflammatory mediators. Although H(1) receptor antagonists are the mainstay of therapy for allergic disease, the unacceptably high incidence of anticholinergic and CNS-related side effects of first-generation H(1) antagonists led to the search for improved second-generation H(1) antagonists. While many of these agents were largely devoid of CNS side effects, their tendency for drug-drug interactions (e.g., terfenadine and astemizole) resulted in an increased incidence of cardiotoxicity. Furthermore, second-generation H(1) antagonists exhibited weak anti-inflammatory properties and had no effect on nasal congestion. These observations emphasised the need for newer anti-allergic agents with a broader spectrum of activity and an improved safety profile. Among the newer H(1) antagonists currently in clinical development, desloratadine and mizolastine are the most widely studied. Both have a rapid onset of action, and desloratadine has demonstrated clinical efficacy in AR, CIU and seasonal asthma. Desloratadine has several advantages over other H(1) antagonists in that it has proven decongestant activity, a sparing effect on the use of bronchodilators…
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