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Thromboxane A2 Inhibition

Therapeutic Potential in Bronchial Asthma

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American Journal of Respiratory Medicine

Abstract

Bronchial asthma is a disease defined by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. In addition to histamine and acetylcholine, recent studies have emphasized the role of arachidonic acid metabolites (leukotrienes, prostaglandins and thromboxane A2) in the pathogenesis of asthma. Among these mediators, thromboxane A2 (TXA2) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A2 is believed to be involved not only in late asthmatic responses but also in bronchial hyperresponsiveness, a typical feature of asthma.

Strategies for inhibition of TXA2 include TXA2 receptor antagonism and thromboxane synthase inhibition. Results of double-blind, placebo-controlled clinical trials have proven the efficacies of the thromboxane receptor antagonist seratrodast and the thromboxane synthase inhibitor ozagrel in the treatment of patients with asthma. Seratrodast and ozagrel are available in Japan for the treatment of asthma. Ramatroban, another thromboxane receptor antagonist, is currently under phase III clinical evaluation in Europe and Japan for the treatment of asthma.

The pharmacological profiles of the thromboxane modulators may be improved by combination with leukotriene D4 receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D4 and thromboxane A2 receptors, may have potent therapeutic effects in the treatment of bronchial asthma. Large scale clinical trials are necessary to further define the role of thromboxane modulators in the treatment of patients with asthma.

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Acknowledgements

The authors wish to acknowledge “la communauté française de Belgique” for their financial support.

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  1. Department of Medicinal Chemistry, University of Liège, avenue de l’Hôpital, 1, B36, B - 4000, Liège, Belgium

    Jean-Michel Dogné, Xavier de Leval, Patricia Benoit & Jacques Delarge

  2. Department of Pharmacy, University of Namur, Namur, Belgium

    Bernard Masereel

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  1. Jean-Michel Dogné
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Dogné, JM., de Leval, X., Benoit, P. et al. Thromboxane A2 Inhibition. Am J Respir Med 1, 11–17 (2002). https://doi.org/10.1007/BF03257158

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