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Thromboxane A2 inhibition: therapeutic potential in bronchial asthma.
Am J Respir Med 2002; 1(1):11-7AJ

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 A(2)) in the pathogenesis of asthma. Among these mediators, thromboxane A(2) (TXA(2)) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A(2) 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 TXA(2) include TXA(2) 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 D(4) receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D(4) and thromboxane A(2)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.

Authors+Show Affiliations

Department of Medicinal Chemistry, University of Liège, Avenue de l'Hôpital 1, B36, B-4000 Liège, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

14720071

Citation

Dogné, Jean-Michel, et al. "Thromboxane A2 Inhibition: Therapeutic Potential in Bronchial Asthma." American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions, vol. 1, no. 1, 2002, pp. 11-7.
Dogné JM, de Leval X, Benoit P, et al. Thromboxane A2 inhibition: therapeutic potential in bronchial asthma. Am J Respir Med. 2002;1(1):11-7.
Dogné, J. M., de Leval, X., Benoit, P., Delarge, J., & Masereel, B. (2002). Thromboxane A2 inhibition: therapeutic potential in bronchial asthma. American Journal of Respiratory Medicine : Drugs, Devices, and Other Interventions, 1(1), pp. 11-7.
Dogné JM, et al. Thromboxane A2 Inhibition: Therapeutic Potential in Bronchial Asthma. Am J Respir Med. 2002;1(1):11-7. PubMed PMID: 14720071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thromboxane A2 inhibition: therapeutic potential in bronchial asthma. AU - Dogné,Jean-Michel, AU - de Leval,Xavier, AU - Benoit,Patricia, AU - Delarge,Jacques, AU - Masereel,Bernard, PY - 2004/1/15/pubmed PY - 2005/5/6/medline PY - 2004/1/15/entrez SP - 11 EP - 7 JF - American journal of respiratory medicine : drugs, devices, and other interventions JO - Am J Respir Med VL - 1 IS - 1 N2 - 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 A(2)) in the pathogenesis of asthma. Among these mediators, thromboxane A(2) (TXA(2)) has attracted attention as an important mediator in the pathophysiology of asthma because of its potent bronchoconstrictive activity. Thromboxane A(2) 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 TXA(2) include TXA(2) 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 D(4) receptor antagonists. A multi-pathway inhibitory agent such as YM 158, which is a novel orally active dual antagonist for leukotriene D(4) and thromboxane A(2)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. SN - 1175-6365 UR - https://www.unboundmedicine.com/medline/citation/14720071/Thromboxane_A2_inhibition:_therapeutic_potential_in_bronchial_asthma_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=14720071.ui DB - PRIME DP - Unbound Medicine ER -