Asthma leukotriene antagonists

Findlay, S.R., Barden, J.M., Easley, C.B. and Glass, M. (1992). Effect of the oral leukotriene antagonist ICI 204,219 on the antgen-induced bronchoconstriction in subjects with asthma. J. Allergy Clin. Immunol. 89, 1040-1045. 

For example, (Ipc)2BCl was found to be an advantageous in the enantioselective reduction in the large-scale preparation of L-699,392, a specific leukotriene antagonist of interest in the treatment of asthma.147... 

Patients receiving these agents may notice improvement in 1 to 2 weeks, but maximal benefit may not be seen for 4 to 6 weeks. Cromolyn and nedocromil appear to be similar in efficacy to the leukotriene antagonists and theophylline for persistent asthma.18 Both agents are well tolerated with adverse effects limited to cough and wheezing. Bad taste and headache have also been reported with nedocromil. One dose of cromolyn or nedocromil prior to exercise or allergen exposure will provide effective prophylaxis for 1 to 2 hours. Cromolyn and nedocromil are not as effective as albuterol for prophylaxis of exercise-induced asthma. 

Holgate ST, Bradding P, Sampson AP. Leukotriene antagonists and synthesis inhibitors new directions in asthma therapy. J Allergy Clin Immunol 1996 98 1-13. 

Currie GP, Lima JJ, Sylvester JE, Lee DK, Cockburn WJ, Lipworth BJ. (2003) Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma. Br J Clin Pharmacol. 56, 422-426. 

Astra Zeneca s ZD 3523 (122),158 a potential leukotriene antagonist for the treatment of asthma, was prepared by an asymmetric hydrogenation of a 96 4 mixture of Z-4,4,4-trifluoro-2-methyl-2-butenoic acid (123) with a ruthenium/TMBTP catalyst (Scheme 12.49). This chemistry has been demonstrated at the multi-100-kg scale.87... 

The peptide leukotrienes 99,100, and 101 cause contraction of the bronchial smooth muscle and probably play an important role as mediators in allergic reactions (e.g. asthma) and inflammations. Antagonistic blockade of the leukotriene action of 99,100, and 101, by analogy with histamine Hj-reccptor antagonists, would therefore be an important principle in the treatment of allergic symptoms. A number of selective peptide leukotriene antagonists have in fact been synthesized by Smith Kline ... 

Krawiec ME, Wenzel SE (1999) Use of leukotriene antagonists in childhood asthma. Curr Opin Pediatr 11 540-547... 

Leukotriene antagonists are a new class of drugs for asthma. An additional... 

Cromolyn and nedocromil are no more or less effective than theophylline or the leukotriene antagonists for persistent asthma. ... 

Dahlen S, Malmstrom K, Nizankowska E, et al. Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist A randomized, double-blind, placebo-controlled trial. Am J Respir Crit care Med 2002 165 9-14. 

Lipoxygenase (ALOX5) Leukotriene receptor antagonists Asthma response... 

Leukotriene Antagonists As noted above, an inhibitor of lipoxygenase (zileuton) and LTD (and LTE ) receptor antagonists (zafirlukast, montelukast) have become available for clinical use. At present, these agents are approved only for use in asthma. 

Subgroups of Antiasthmatic Drugs Drugs useful in asthma include bronchodilators (smooth muscle relaxants) and anti-inflammatory drugs (Figure 20-2). Leukotriene antagonists may have both bronchodilator and anti-inflammatory properties. 

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