Biosynthesis inhibitors for leukotrienes in bronchial asthma

Abstract

This article reviews the literature on the effects of leukotrienes in asthma. In particular, the ability of recently developed synthesis inhibitors to attenuate the asthma causing effects of leukotrienes is examined. MEDLINE (1966-1996), EMBASE (Excerpta Medica; 1974-1996), and other biomedical and drug directory databases were searched to identify English-language articles (basic science, clinical trial research, and review articles) and abstracts of conference proceedings on biosynthesis inhibitors for leukotrienes and related terms. Leukotrienes are endogenous molecules formed by the breakdown of a membrane constituent, arachidonic acid, via the 5-Lipoxygenase enzyme pathway. This pathway ultimately produces several species of leukotrienes with various biologic activities, including generalized inflammatory effects associated with asthma: increased vascular permeability, enhanced mucous production, and decreased mucociliary transport. The biosynthesis inhibitors for leukotrienes attenuated the response to inhaled leukotrienes and allergen challenges (MK-0591; MK-886; AA-681; A-64077; ZD-2138). These agents produced beneficial effects in cold, exercise (A-64077) and aspirin-induced asthma (A-64077; ZD-2138), as well as clinical asthma. Many of these medications appear to be effective in the treatment of asthma (BAYX-1005; MK-0591; MK-886; AA-681; A-64077; ZD-2138; U-60257; FR-110302; BI-6239; A-78773; ABT-761; L-746530; L-699333; ZM-230487). Further clinical research is needed to determine which patients would benefit most from their use.