ABSTRACT
The current interest in leukotriene-receptor antagonists can be traced back to 1938 when Feldberg and Kellaway 1 first demonstrated that stimulated lung tissue produces a material which slowly induces sustained contractions of guinea-pig smooth muscle. The contractions were different from those induced by histamine and the material was referred to as slowreacting substance (SRS). Two years later Kellaway and Trethewie 2 showed that a similar material was released from the guinea-pig pulmonary system upon immunological challenge. Brocklehurst, 3 in 1960 first used the term "slow-reacting substance of anaphylaxis (SRS A)" to describe material produced by guinea-pig or human lungs following immunological challenge by antigens. Although the structure of SRS-A was not known, the crude material was intensively studied during the next 20 years in a number of laboratories, including those of Austen, Orange, Bach, Ishizaka, Parker, Piper, and Lichtenstein. 4-12 This work led to the appreciation of the circumstances leading to SRS-A release and emphasized the potential importance of SRS-A in the pathogenesis of bronchial asthma. However, the significance of SRS-A in allergy and inflammation awaited two events: the determination of its chemical structure and the discovery of an effective receptor antagonist.
