Fluorine Eliminate The Impact Of Acid On Arachidonic Acid Metabolism

Leukotrienes (LTs) have been found to be a group of very important metabolites of arachidonic acid through the 5-lipoxygenase pathway. Among these metabolites, LTB₄ is a potent inflammatory mediator with founctions such as induction of leukocyte accumulation, mediation of vascular permeability changes and mediation of pain responses. LTC₄, LTD₄ and LTE₄ have been demonstratedas the active components of slow reacting substance of anaphylaxis (SRS-A), which contribute to asthma by inducing contraction of airway smooth muscle, increasing mucin release and inhibiting the activity of human cilia.Steroidal anti-inflammatory drugs have strong anti-inflammatory activities on diseases in which LTs are considered to be involved because these drugs can inhibit the activity of phospholipase, prevent release of arachidonic acid from the phospholipid membrane, and in turn, inhibit the formation of PGs, TXA₂ and LTs. However, the poor selectivity limits them to be widely used in clinical therapies.Indomethacin,one of the nonsteroidal anti-inflammatory drugs, has no effect on 5-lipoxygenase activity so that it can not inhibit the formation of LTs. Recently, U-60257, a derivative of PGI, was found to be a selective 5-lipoxygenase inhibitor and can inhibit the formation of LTs. Unfortunately, there was a report that it can not prevent the bronchoconstriction when asthmatics were challenged with antigen. The reason may be that blocking the 5-lipoxygenase pathway shunts arachidonic acid toward increased formation of the bronchoconstrictor of cyclo-oxygenase products such as PGD_?. So these non-steroidal agents which can inhibit both the 5-lipoxygenase and cyclo-oxygenase activities may be more effective in the treatment of inflammations. Agents which can block the activity of leukotrienes may be developed to be drugs of choice in therapies of inflammations or asthma. The major purpose...