Cysteinyl leukotriene antagonist Zafirlukast

The biological actions of the cysteinyl leukotrienes are mediated via stimulation of CysLTi receptors. Montelukast and zafirlukast are competitive antagonists of these receptors. In contrast, zileuton suppresses synthesis of the leukotrienes by inhibiting 5-lipoxygenase, a key enzyme in the bioconversion of arachidonic acid to the leukotrienes. Zileuton also blocks the production of leukotriene B4, another arachidonic acid metabolite with proinfiammatory activity. The CysLTi-receptor antagonists alter neither the production nor the actions of leukotriene B4. 

The leukotriene receptor antagonists are antagonists of cysteinyl leukotrienes at CysLTi receptors and include zafirlukast, montelukast, and pranlukast. 

Two clinically distinct cysteinyl leukotriene receptor antagonists (zafirlukast and montelukast) and one inhihitor of leukotriene synthesis (zUeuton) have been available in the United States since 1996 for both children and adults with persistent asthma. In challenge studies, they reduce allergen-, exercise-, cold-air hyperventilation-, irritant-, and aspirin-induced asthma. Chnical use of zileuton is limited owing to the need for four-times-daily dosing, the potential for elevated liver enzymes (especially in the first 3 months of therapy), and the potential inhibition of drugs metabolized by the CYP3A4 isoenzymes. ... 

Zafirlukast is an oral leukotriene receptor antagonist (LTRA) for the treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLTl receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages. 

Many specific mediator receptors are involved in asthma but they are so abundant that specific antagonists for these receptors have little effect, with an exception for cysteinyl leukotriene-1 (cys-LTj) receptors which are distributed predominantly on airway smooth muscle and (to a lesser extent) on macrophages. Their numbers are small, however, and this may explain why antileukotrienes like montelukast and zafirlukast, which prevent predominantly leukotriene-induced bronchoconstriction, are less effective than P2-agonists. 

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