Leukotrienes and their antagonists in allergic disorders.
Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of allergic rhinitis and asthma. Strategies for inhibition of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. The leukotrienes antagonists, with particular reference to asthma and allergic rhinitis, is reviewed in this paper. In 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 LY-171883, SK&F-104353, ICI-204219, ONO-1078, MK-751, MK-0679, 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. NZ-107 was studied for its effect on airway inflammation caused by intratracheal injection of LTB4 or IL-5, or by inhalation of PAF, and by cell activation. Analysis of the BAL fluid revealed that both induced eosinophilia and neutrophilia were suppressed. Surprisingly, although PAF and superoxide generation were inhibited in macrophages and eosinophils, NZ-107 had no effect on neutrophil activation. U-75302 was studied in guinea pigs and inhibited LTB4 induced chemotaxis of eosinophils in vitro and antigen-induced lung eosinophilia in vivo. Further studies are needed to clarify the exact mechanism by which these compounds provide beneficial effects.
Negro
J M
JM
Allergology Section, H.U. Virgen de la Arrixaca, El Palmar, Murcia, Spain.
Miralles
J C
JC
Ortiz
J L
JL
Funes
E
E
García
A
A
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D005541:Forced Expiratory Volume / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000378:metabolism*; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D015394:Molecular Structure; D018077:Receptors, Leukotriene / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000188:drug therapy / Q000378:metabolism
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D018077:Receptors, Leukotriene