Description
SQ 29,548 is a highly selective TP receptor antagonist which binds to the human recombinant TP receptor with a Ki of 4.1 nM. It inhibits the aggregation of washed human platelets induced by U-46619 with an IC50 of 0.06 μM. It antagonizes U-46619 induced contraction of rat and guinea pig tracheal, arterial, and venous smooth muscles with drug/receptor dissociation constants (KB) in the range of 0.5-1.7 nM. SQ 29,548 also inhibits the contraction of rat vascular smooth muscle induced by 8-iso PGF2α.
Uses
SQ-29548 is a potent and selective thromboxane A2 receptor antagonist.
in vitro
in guinea-pig trachea and rat aorta, sq 29,548 competitively antagonized the activity of 9,11-azo pgh2 with pa2 values of 7.8 and 8.4, respectively. sq 29,548 competitively antagonized contractions of guinea-pig tracheal spirals induced by 11,9-epoxymethano pgh2 with the pa2 value of 9.1. the sq 29,548 competitively antagonized tracheal induced by 11,9-epoxymethano pgh2 and pgd2 with the pa2 values of 8.2 and 8.3, respectively. sq 29,548 partially antagonized the contractions of guinea-pig tracheal spirals caused by pge2. sq 29,548 significantly inhibited the aorta contracting activity of 11,9-epoxymethano pgh2 (pa2 = 9.1) and thromboxane a2 released from perfused guinea-pig lungs upon arachidonic acid challenge [1].
in vivo
in anesthetized dogs, sq 29,548 (0.2 mg/kg/h) completely inhibited the vasoconstrictor response of the left circumflex coronary artery (lcx) caused by u-46619. sq 28,585 showed no effects on infarct size as compared with vehicle controls [3]. in sham mi rats, treatment with sq-29,548 significantly blunted this loss of ck activity and amino-nitrogen concentration from the ischemic myocardium. sq-29,548 significantly prevented the extension of ischemic damage in the myocardium and improved survival following acute coronary artery ligation [4].
References
[1] ogletree m l, harris d n, greenberg r, et al. pharmacological actions of sq 29,548, a novel selective thromboxane antagonist[j]. journal of pharmacology and experimental therapeutics, 1985, 234(2): 435-441.
[2] abe t, takeuchi k, takahashi n, et al. rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization[j]. journal of clinical investigation, 1995, 96(2): 657.
[3] grover g j, schumacher w a. effect of the thromboxane receptor antagonist sq 29,548 on myocardial infarct size in dogs[j]. journal of cardiovascular pharmacology, 1988, 11(1): 29-35.
[4] hock c e, brezinski m e, lefer a m. anti-ischemic actions of a new thromboxane receptor antagonist, sq-29,548, in acute myocardial ischemia[j]. european journal of pharmacology, 1986, 122(2): 213-219.
