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 (beta(2)-agonists) and a low potential for drug interactions. The broad anti-inflammatory properties of
desloratadine and
mizolastine, which distinguish these agents from other H(1) antagonists in clinical development (e.g.,
norastemizole and
levocetirizine), suggest they may have a more profound impact on the underlying disease in patients suffering from different forms of
allergy. The lack of clinical efficacy and safety data on
rupatadine and
HSR-609, both novel H(1) antagonists, precludes an accurate assessment of their potential for treating allergic disease.
Epinastine and
efletirizine are being developed exclusively for topical application and are unlikely to play a significant role in the management of allergic diseases as a whole.