Predicting and Establishing the Clinical Efficacy of a Histamine H1-Receptor Antagonist

Desloratadine, the Model Paradigm

Glenis Scadding


Clin Drug Invest. 2005;25(3):153-164. 

In This Article


The drug development process is essential to provide an indication of the pharmacotherapeutic potential of an antihistamine and to establish its clinical efficacy. In vitro tests have demonstrated that second-generation antihistamines have improved H1-receptor specificity and a slower dissociation rate compared with first-generation antihistamines; second-generation agents also display noncompetitive antagonism. Studies of antihistamines in animal models have provided in vivo evidence of their antihistaminic, antiallergic and anti-inflammatory properties. Collectively, results from preclinical studies provide insight into the possible mechanisms of the antiallergic and anti-inflammatory activities of these agents.

Investigational models like the histamine-induced skin wheal-and-flare model are limited in predicting the efficacy of an antihistamine. Although this model has been widely used, it measures only antihistamine activity, mimics only the early phase of the allergic response, does not reflect the systemic inflammatory process underlying allergic disease, and may not be an appropriate indicator of clinical efficacy. Allergen chamber studies are a reproducible method assessing the response to antihistamine therapy under controlled conditions. These studies, however, are generally limited in duration and by the size of the study population. Although studies throughout the developmental process may indicate the potential of an antihistamine and possibly its mechanisms of action in the treatment of allergic disease, well controlled pivotal trials are the most accurate indicator of the effectiveness of an H1-receptor antagonist in clinical practice.

For the antihistamine desloratadine, in vitro studies have revealed it to be a highly potent H1-receptor antagonist and inhibitor of inflammatory mediators. Animal models with desloratadine have exhibited both antiallergic and anti-inflammatory properties. Under controlled chamber conditions, it rapidly improved symptoms of SAR. Ultimately, clinical trials have established that desloratadine is effective in reducing the symptoms of SAR, including nasal obstruction, a symptom that does not usually respond to antihistamine treatment. In CIU, desloratadine has a rapid onset of action and a durable effect. Additionally, the results of a large observational study of patients with SAR confirmed the efficacy and safety of desloratadine in a 'real world' clinical setting.