Leukotriene receptor antagonists and biosynthesis inhibitors: potential breakthrough in asthma therapy

Effect of Dietary Supplementation with Polyunsaturated Fatty Acids on Bronchial Hyperreactivity in Subjects with Seasonal Asthma

“…Two fundamental strategies have been followed for the pharmacological control of leukotriene metabolism: inhibition of their synthesis and release and selective antagonism of their receptors [13]. We tried a third strategy to reduce bronchial reactivity in atopic patients: the administration of a substrate different from arachidonic acid, with the aim of suppressing or reducing the production of leukotrienes via the 5-lipoxygenase pathway.…”

Role of leukotrienes in asthma pathophysiology

“…LTC 4 is enzymatically converted to LTD 4 , and subsequently LTE 4 . 3,8,9 Although LTB 4 has important functions in cellular recruitment, its role in asthma has not been well defined, and this leukotriene will not be discussed further in this review.…”

“…8,86 Zileuton (A-64077), an N-hydroxyurea derivative, is probably the most extensively studied 5-LO inhibitor. In humans, it has been found effective in inhibiting bronchoconstriction induced by cold, dry air, and aspirin-induced asthma.…”

The role of new asthma treatments

“…Inhibitors of cysteinyl leukotriene synthesis or leukotriene receptor antagonists such as zileuton, zafirlukast, pranlukast and montelukast are available for prescription, although their exact place in asthma management has not been determined in many countries. 33 Regarding the development of mediator antagonists in asthma, it is of interest to note that other mediator antagonists apart from leukotriene antagonists have not been shown to be clinically effective in asthma: for instance, platelet-activating factor, thromboxane and bradykinin receptor antagonists. Cysteinyl-leukotrienes are important mediators of asthma, participating in bronchoconstriction, airway microvascular leakage and probably in eosinophil recruitment in asthma.…”