SQ 29,548

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Background

SQ 29,548 is a novel and selective thromboxane antagonist [1]. Thromboxane belongs to a family of lipids involved in clot formation (thrombosis). Thromboxane is a vasoconstrictor and a potent hypertensive agent which facilitates platelet aggregation [2].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].

[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.