Antileukotrienes in clinical development for asthma

Asthma is a serious world health problem characterised by a chronic inflammatory disorder of the airways. Asthma attacks, or exacerbations, are episodic but airway inflammation is chronically present. Thus, this disorder requires long-term management. The goals of asthma management include prevention steps for long-term control, action steps to stop attacks, recognising deteriorating asthma, how to treat deteriorating asthma, how and when to seek medical attention and education. In order to achieve the best therapeutic choice, a stepwise approach should be adopted. In recent years, much progress regarding the characterisation of leukotrienes (LTs) has been achieved. These substances are important products of action of the 5-lipoxygenase (5-LO) enzyme on arachidonic acid (AA) and it has been established that the leukotrienes are key mediators of both allergy and inflammation. Consequently, the important role of the cysteinyl-leukotrienes (Cys-LTs) in the pathophysiology of bronchial asthma has been suggested. Pharmacological support for the role of Cys-LTs in asthma has been observed using inhibitors of 5-LO and specific LT receptor antagonists. In the clinical setting, the LT receptor, which plays the most important role, is the Cys-LT1 receptor. The antagonists of this receptor have proven an effective therapy in chronic asthmatics, agonist antigens and exercise-induced bronchoconstriction and in aspirin-intolerant asthmatics. These drugs provide a new approach in asthmatic therapy and therefore may facilitate the compliance of daily therapy.