Leukotriene modifiers in the treatment of asthma

BMJ 1998; 316 doi: https://doi.org/10.1136/bmj.316.7140.1257 (Published 25 April 1998) Cite this as: BMJ 1998;316:1257

Look promising across the board of asthma severity

  1. Anthony Sampson, Lecturer,
  2. Stephen Holgate, MRC clinical professor
  1. Immunopharmacology Group, Southampton General Hospital, Southampton SO16 6YD

    Leukotriene modifiers are an entirely new class of asthma treatment, which have entered clinical practice in 1996-7 in several countries including Britain, Japan, and the United States. Their development is an example of rational drug design following the elucidation of leukotriene structures in 1979-80 and the subsequent confirmation of their pathophysiological role as inflammatory mediators in asthma.1

    There are two types of leukotriene modifier: leukotriene synthesis inhibitors and cysteinyl leukotriene receptor antagonists.2 Both are used to block the bronchoconstrictor and pro-inflammatory activity of cysteinyl leukotrienes within the asthmatic airway. Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) were originally identified as long lasting smooth muscle spasmogens and collectively termed “slow reacting substance of anaphylaxis” (SRS-A). They are now known to be metabolites of arachidonic acid formed by the 5-lipoxygenase pathway1 and are produced almost exclusively by inflammatory leucocytes, especially mast cells, basophils, and eosinophils. The leukotriene receptor antagonists block the activity of cysteinyl leukotrienes at their receptors (CysLT1) on bronchial smooth muscle and elsewhere, while the leukotriene synthesis inhibitors block the synthesis of all leukotrienes by interrupting the 5-lipoxygenase pathway.2

    Cysteinyl leukotrienes are among …

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