Leukotriene Receptor Antagonists and Biosynthesis Inhibitors in Asthma

Abstract

The 5-lipoxygenase metabolites of arachidonic acid, leukotrienes B4, C4, D4 and E4, are potent pro-inflammatory mediators that are implicated in the pathophysiology of asthma. Therefore, many antileukotriene compounds have been developed. Two major categories of these drugs are presently under investigation in patients with asthma: (a) leukotriene D4 receptor antagonists, which block the effects of cysteinyl leukotrienes at the receptor site; (b) leukotriene biosynthesis inhibitors, which prevent the formation of both cysteinyl leukotrienes and leukotriene B4. Both categories provide clinically relevant protection against bronchoconstrictor stimuli, such as exercise, cold dry air, and aspirin (acetylsalicylic acid). Unexpectedly, in allergen inhalation studies, leukotriene receptor antagonists have been shown to be more effective than the biosynthesis inhibitors. Consequently, owing to their favourable pharmacokinetic profile, potent antileukotriene drugs represent a potential first-line treatment in the management of certain types of asthma such as exercise and aspirin-induced asthma. However, the definite place in therapy of both categories of drugs will depend on the results of long term treatment in the various subgroups of asthmatic patients in comparison with and in addition to present antiasthma medication.