Leukotriene receptor antagonists and biosynthesis inhibitors: potential breakthrough in asthma therapy.
Cysteinyl leukotrienes are potent bronchoconstrictors, inducers of airway microvascular leakage and oedema, and of mucus secretion, in addition to causing an eosinophilic airway infiltration. Increased urinary excretion of the cysteinyl leukotriene E4 (LTE4) has been demonstrated following allergen challenge and during acute asthma attacks. Strategies for inhibition of cysteinyl leukotriene effects include antagonism of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. In experimental challenge studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as ICI 204,219 and MK-571, and synthesis inhibitors, such as zileuton, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. Further studies are needed to clarify the exact mechanisms by which these compounds provide beneficial effects. Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of asthma.
Chung
K F
KF
Dept of Thoracic Medicine, National Heart & Lung Institute, Royal Brompton National Heart & Lung Hospital, London, UK.
D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D006801:Humans; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D018927:Anti-Asthmatic Agents; D020024:Leukotriene Antagonists; D016859:Lipoxygenase Inhibitors