Leukotriene synthesis inhibitors versus antagonists: the pros and cons.
It has been recognized for many years that leukotrienes play an important role in mediating various effects of the allergic reaction. Recent evidence has shown that they play a role in other diseases. Leukotrienes can be separated into the fairly well-characterized cysteinyl leukotrienes and the less well-characterized leukotriene B(4). Effects of the leukotrienes are mediated through receptors that are expressed on a variety of cell types and can be modulated based on the inflammatory environment present. The pharmaceutical industry has long been interested in blocking leukotriene action. As such, two approaches have been developed that led to drugs approved for treating allergic disease. The most widely used class is the cysteinyl type 1 receptor antagonists, which block binding of the cysteinyl leukotrienes to the cell. The second class is an inhibitor of the 5-lipoxygenase enzyme that prevents synthesis of both the cysteinyl leukotrienes and leukotriene B(4). This review focuses on the role that leukotrienes play in various diseases, with the emphasis on allergic diseases, and considers the rationale for choosing either a leukotriene antagonist or synthesis inhibitor as a treatment option.
Steinke
John W
JW
Asthma and Allergic Disease Center, Beirne Carter Center for Immunology Research, University of Virginia Health System, Charlottesville, VA 22908-1355, USA. js3ch@virginia.edu
Culp
Jeffrey A
JA
D000085:Acetates / Q000627:therapeutic use; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001094:Arachidonate 5-Lipoxygenase / Q000502:physiology; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D002867:Chromones / Q000627:therapeutic use; D003521:Cyclopropanes; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D015289:Leukotrienes / Q000096:biosynthesis* / Q000502:physiology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048448:Phenylcarbamates; D011804:Quinolines / Q000627:therapeutic use; D018077:Receptors, Leukotriene / Q000502:physiology*; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000627:therapeutic use
D000085:Acetates; D018927:Anti-Asthmatic Agents; D002867:Chromones; D003521:Cyclopropanes; D007211:Indoles; D018836:Inflammation Mediators; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D048448:Phenylcarbamates; D011804:Quinolines; D018077:Receptors, Leukotriene; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; D001094:Arachidonate 5-Lipoxygenase; C093875:montelukast; C047681:pranlukast; C062735:zafirlukast