Therapeutic potential of thromboxane inhibitors in asthma

Abstract

This paper reviews the role of thromboxane A₂ (TXA₂) in the pathogenesis of pulmonary allergies, particularly asthma. The potential of TXA₂ modifiers in the prevention and/or treatment of pulmonary allergies is also discussed. Bronchial asthma is characterised by reversible airway obstruction, bronchial hyperresponsiveness and inflammation. Several studies have elucidated the role of arachidonic acid metabolites (leukotrienes, prostaglandins and TXA₂) in the pathogenesis of asthma. Among those mediators, TXA₂ has attracted attention due to its strong physiological activity. Indeed, TXA₂ demonstrates not only potent bronchoconstrictive activity but is also believed to be involved both in late asthmatic responses and in bronchial hyperresponsiveness, a typical feature of this disease. Several thromboxane receptor antagonists (TXRAs) and thromboxane synthase inhibitors (TXSIs) have been studied with the aim of reducing or preventing asthma. As double-blind, placebo-controlled clinical trials have proven the efficiency of some TXA₂ modifiers in treating asthma, the TP receptor antagonist seratrodast (AA-2414) and the thromboxane synthase inhibitor ozagrel hydrochloride (OKY-046) are now available as anti-asthmatic agents in Japan. Moreover, seratrodast and ramatroban (BAY-U-3405), another thromboxane receptor antagonist, are currently under Phase III clinical evaluation in the US for the treatment of asthma.

• asthma
• thromboxane A2
• thromboxane inhibitors
• thromboxane modulators