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Chemical Compound Review

OZAGREL HCl     (E)-3-[4-(imidazol-1- ylmethyl)phenyl]prop...

Synonyms: SureCN36182, CHEMBL542549, O1385_SIGMA, CCG-100969, SBB066152, ...
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Disease relevance of ozagrel

  • Effects of OKY 046, a thromboxane-synthase inhibitor, on renal function in nonazotemic cirrhotic patients with ascites [1].
  • However, insulin clearance was not significantly affected by OKY-046, implying that inhibition of Tx synthetase reduced proteinuria independently of changes in renal hemodynamics [2].
  • Pretreatment with a lower molecular weight imidazole derivative OKY 046 (N = 9) inhibited all Tx synthesis after ischemia [3].
  • Histologically, the liver preserved for 6 hr in simple cold lactated Ringer's solution exhibited interstitial edema, various degrees of hepatocyte swelling, and sinusoidal stenosis, as well as dilatation, while the livers treated with OKY-046 demonstrated much less hepatocyte swelling, and change in sinusoidal width was nearly absent [4].
  • The triphasic relationship between ipsilateral renal blood flow and ureteral pressure previously found following unilateral ureteral obstruction was observed despite OKY-046 infusion [5].

High impact information on ozagrel

  • Pretreatment with the Tx synthetase inhibitor OKY 046 (n = 7) lowered baseline plasma and lymph TxB2 levels to 22 and 52 pg/ml (P less than 0.05) and prevented the IL-2-induced increase in plasma and lung lymph TxB2 (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)[6]
  • We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release [7].
  • In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-beta mRNA levels [8].
  • Pretreatment with OKY-046 led to reduced TxB2 levels of 149 +/- 17 pg/mL, normal lung histology, and 83 +/- 13 PMN/20 HPF, a value similar to that of the sham group and lower than that of the placebo-treated group (p less than 0.05) [9].
  • Prior to tourniquet inflation, both OKY 046 and ketoconazole lowered plasma TxB2 levels as well as the L/P ratio (p less than 0.05) [3].

Chemical compound and disease context of ozagrel

  • The effect of the thromboxane A2 synthesis inhibitor OKY-046 on renal function in rabbits following release of unilateral ureteral obstruction [10].
  • In patients with chronic bronchitis, the cough threshold was significantly greater with indomethacin (5.94 (GSEM 1.50) microM) than with placebo (3.41 (GSEM 1.33) microM and OKY-046 2.97 (GSEM 1.43) microM) [11].
  • The reduction in thromboxane A2 production associated with increased prostacyclin appeared to be the major mechanism of the interruption of the thrombus formation by OKY-046 [12].
  • In contrast, both inhibition of Tx synthesis (Tx < 3 ng/ml) with OKY-046 and blockade of the Tx receptor with SQ-30741 (Tx > 20 ng/ml) were not only associated with significantly lower peak PVRs (<0.2 cmH2O x ml(-1) x min) but also with attenuated increase in lung wet-to-dry ratio and airway edema [13].
  • Pretreatment with OKY-046 (100 mg/kg i.v., n = 8) prevented PMA-induced increases in TxB2, LTB4, and pulmonary edema formation but did not prevent the increase in PVR.(ABSTRACT TRUNCATED AT 250 WORDS)[14]

Biological context of ozagrel


Anatomical context of ozagrel

  • Maximal degranulation of atypical mast cells was delayed to 6 hours with OKY-046, whereas these cells responded completely at 1 hour without OKY-046 [19].
  • We conclude that OKY-046 reduces post-preservation reoxygenation injury by protecting sinusoidal endothelial cells and hepatocytes [4].
  • The frequency of antidonor precursor cytotoxic T cells (pCTL), as measured by limiting dilution assay, was consistently lower in allografts from OKY-046-treated animals (1/3146-1/5160) compared with vehicle treatment (1/661-1/1878), while no difference in pCTL ranges were seen in splenocytes from both groups [20].
  • Tracheas were also pretreated with meclofenamate (10(-6) M) (a cyclooxygenase inhibitor) and UK 37,248 (10(-8) to 10(-5) M) and OKY 046 (10(-9) to 10(-6) M) (thromboxane synthetase inhibitors), and the thiamylal protocol was repeated [21].
  • These changes were completely blocked in the OKY-046 group, except for the neutrophil depletion and the increase in lung lymphatic flow [22].

Associations of ozagrel with other chemical compounds

  • We conclude that OKY-046 alters the antigen-induced response of atypical mast cells, the subsequent cellular and clinical late-phase response, and prevents the increase in histamine response [19].
  • Platelet aggregation and thromboxane B2 (TXB2) formation induced by collagen and arachidonic acid were suppressed by the infusion of OKY-046, while both were not affected by the infusion of vehicle [23].
  • Bradykinin instilled by the airway route significantly decreased systemic blood pressure but this effect was not altered in animals pretreated with either indomethacin or OKY-046 [24].
  • CONCLUSIONS: We have demonstrated that atherosclerosis in aortic allografts is inhibited by the continuous administration of either OP-2507 or OKY-046, and a combination of both agents strongly increases this inhibitory effect [25].
  • Immunoglobulin E-mediated bronchoconstriction in actively sensitized rats was also inhibited by both DP-1904 (1, 10 mg/kg) and OKY-046 (100 mg/kg) [26].

Gene context of ozagrel

  • In the next series of experiments, ET-1 and ET-3 were administered after administration of 20 mg/kg of OKY-046 [27].
  • OKY-046 showed no effects in animals treated with ET-1, as in those pre-treated with INDO, while it significantly inhibited the decreases in hepatic blood flow induced by ET-3 [27].
  • Indomethacin and OKY-046 did not, however, reduce 125I-EGF binding [28].
  • The administration of OKY-046 (inhibitor of TXA2 synthesis) to the University of Wisconsin solution suppressed this reduction in TXA2R number [29].
  • OKY-046 also increased PCNA expression in the cortex and outer stripe in Sham-Nx animals [30].

Analytical, diagnostic and therapeutic context of ozagrel

  • Reduced protein excretion (0.88 +/- 0.12 mg/min/g, n = 6, P less than 0.001) also occurred with inhibition of Tx synthetase by OKY-046, 10(-4) M, a dose that was shown in separate perfusions to inhibit urinary TxB2 excretion by greater than 85% [2].
  • The addition of OKY-046 to the preservation solution, however, prevented the rise in reperfusion pressure almost completely and the increase in effluent enzyme levels [29].
  • Despite the beneficial effects on allograft function, OKY-046 neither altered the morphologic appearance of the cellular infiltrate nor the systemic proliferative and cytotoxic anti-donor cellular immune responses [31].
  • Six days following transplantation, renal TXB2 production was only partially inhibited in animals given continuous infusions of OKY-046, and remained markedly elevated [31].
  • Chronic oral administration of OKY-046 ameliorated not only the renal hyperperfusion but increased urinary albumin excretion (UAE) at two weeks, but also the renal hypoperfusion, filtration fraction and UAE at 24 weeks [32].


  1. Effects of OKY 046, a thromboxane-synthase inhibitor, on renal function in nonazotemic cirrhotic patients with ascites. Gentilini, P., Laffi, G., Meacci, E., La Villa, G., Cominelli, F., Pinzani, M., Buzzelli, G. Gastroenterology (1988) [Pubmed]
  2. A role for thromboxane in complement-mediated glomerular injury. Cybulsky, A.V., Lieberthal, W., Quigg, R.J., Rennke, H.G., Salant, D.J. Am. J. Pathol. (1987) [Pubmed]
  3. Thromboxane A2 moderates permeability after limb ischemia. Lelcuk, S., Alexander, F., Valeri, C.R., Shepro, D., Hechtman, H.B. Ann. Surg. (1985) [Pubmed]
  4. Beneficial effect of thromboxane A2 synthetase inhibitor on cold-stored rat liver. Suehiro, T., Yanaga, K., Itasaka, H., Kishikawa, K., Shirabe, K., Sugimachi, K. Transplantation (1994) [Pubmed]
  5. Effect of thromboxane inhibition on renal blood flow in dogs with complete unilateral ureteral obstruction. Loo, M.H., Marion, D.N., Vaughan, E.D., Felsen, D., Albanese, C.T. J. Urol. (1986) [Pubmed]
  6. Role of thromboxane in interleukin 2-induced lung injury in sheep. Klausner, J.M., Paterson, I.S., Morel, N.M., Goldman, G., Gray, A.D., Valeri, R., Eberlein, T.J., Shepro, D., Hechtman, H.B. Cancer Res. (1989) [Pubmed]
  7. Effects of thromboxane A2 inhibition on osteogenic sarcoma cell-induced platelet aggregation. Mehta, P., Lawson, D., Ward, M.B., Lee-Ambrose, L., Kimura, A. Cancer Res. (1986) [Pubmed]
  8. Regulatory role of eicosanoids in extracellular matrix overproduction induced by long-term exposure to high glucose in cultured rat mesangial cells. Pricci, F., Pugliese, G., Menè, P., Romeo, G., Romano, G., Galli, G., Casini, A., Rotella, C.M., DiMario, U., Pugliese, F. Diabetologia (1996) [Pubmed]
  9. Pulmonary leukosequestration induced by hind limb ischemia. Anner, H., Kaufman, R.P., Kobzik, L., Valeri, C.R., Shepro, D., Hechtman, H.B. Ann. Surg. (1987) [Pubmed]
  10. The effect of the thromboxane A2 synthesis inhibitor OKY-046 on renal function in rabbits following release of unilateral ureteral obstruction. Loo, M.H., Egan, D., Vaughan, E.D., Marion, D., Felsen, D., Weisman, S. J. Urol. (1987) [Pubmed]
  11. Prostanoids and cough response to capsaicin in asthma and chronic bronchitis. Fujimura, M., Kamio, Y., Kasahara, K., Bando, T., Hashimoto, T., Matsuda, T. Eur. Respir. J. (1995) [Pubmed]
  12. Development of an experimental model of acute myocardial infarction and the effects of a thromboxane synthetase inhibitor (OKY-046). Tomoda, H. Am. Heart J. (1986) [Pubmed]
  13. Thromboxane mediates pulmonary hypertension and lung inflammation during hyperacute lung rejection. Collins, B.J., Blum, M.G., Parker, R.E., Chang, A.C., Blair, K.S., Zorn, G.L., Christman, B.W., Pierson, R.N. J. Appl. Physiol. (2001) [Pubmed]
  14. OKY-046 prevents increases in LTB4 and pulmonary edema in phorbol ester-induced lung injury in dogs. Sprague, R.S., Stephenson, A.H., Lonigro, A.J. J. Appl. Physiol. (1992) [Pubmed]
  15. Thromboxane synthesis and blood pressure in spontaneously hypertensive rats. Purkerson, M.L., Martin, K.J., Yates, J., Kissane, J.M., Klahr, S. Hypertension (1986) [Pubmed]
  16. Thromboxane and vascular smooth muscle cell growth in genetically hypertensive rats. Ishimitsu, T., Uehara, Y., Ishii, M., Ikeda, T., Matsuoka, H., Sugimoto, T. Hypertension (1988) [Pubmed]
  17. Effects of a thromboxane synthetase inhibitor (OKY-046) and a lipoxygenase inhibitor (AA-861) on bronchial responsiveness to acetylcholine in asthmatic subjects. Fujimura, M., Sasaki, F., Nakatsumi, Y., Takahashi, Y., Hifumi, S., Taga, K., Mifune, J., Tanaka, T., Matsuda, T. Thorax (1986) [Pubmed]
  18. Selective thromboxane A2 synthase inhibition by OKY-046 prevents cardiopulmonary dysfunction after ovine smoke inhalation injury. Westphal, M., Noshima, S., Isago, T., Fujioka, K., Maybauer, M.O., Maybauer, D.M., Traber, L.D., Flynn, J.T., Westphal-Varghese, B.B., Traber, D.L. Anesthesiology (2005) [Pubmed]
  19. Inhibition of the cutaneous response to antigen by a thromboxane-synthetase inhibitor (OKY-046) in allergic dogs. Becker, A.B., Chung, K.F., Aizawa, H., Frick, O.L., Gold, W.M. J. Allergy Clin. Immunol. (1989) [Pubmed]
  20. Association of chronic thromboxane inhibition with reduced in situ cytotoxic T cell activity in rejecting rat renal allografts. Ruiz, P., Coffman, T.M., Klotman, P.E., Sanfilippo, F. Transplantation (1989) [Pubmed]
  21. Contractile responses of guinea pig trachea to oxybarbiturates and thiobarbiturates. Curry, C., Lenox, W.C., Spannhake, E.W., Hirshman, C.A. Anesthesiology (1991) [Pubmed]
  22. Effect of a thromboxane synthetase inhibitor on protamine-induced circulatory changes in sheep. Sugi, K., Esato, K. Surgery (1993) [Pubmed]
  23. Effect of the infusion of OKY-046, a thromboxane A2 synthase inhibitor, on urinary metabolites of prostacyclin and thromboxane A2 in healthy human subjects. Morio, H., Hirai, A., Terano, T., Tamura, Y., Yoshida, S. Thromb. Haemost. (1993) [Pubmed]
  24. Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase. Arakawa, H., Kawikova, I., Löfdahl, C.G., Lötvall, J. Eur. J. Pharmacol. (1992) [Pubmed]
  25. The combined use of prostaglandin I2 analogue (OP-2507) and thromboxane A2 synthetase inhibitor (OKY-046) strongly inhibits atherosclerosis of aortic allografts in rats. Hirano, T., Nakafusa, Y., Kawano, R., Motoyama, K., Arima, T., Sugitani, A., Tanaka, M. Surgery (2001) [Pubmed]
  26. Effect of DP-1904, a thromboxane synthetase inhibitor, on antigen- and spasmogen-induced bronchoconstriction in rodents. Takami, M., Tsukada, W. Eur. J. Pharmacol. (1999) [Pubmed]
  27. Relationship between endothelin and thromboxane A2 in rat liver microcirculation. Kurihara, T., Akimoto, M., Kurokawa, K., Ishiguro, H., Niimi, A., Maeda, A., Sigemoto, M., Yamashita, K., Yokoyama, I., Hirayama, Y. Life Sci. (1992) [Pubmed]
  28. Eicosanoids enhance epidermal growth factor receptor activation and proliferation in glomerular epithelial cells. Cybulsky, A.V., Goodyer, P.R., Cyr, M.D., McTavish, A.J. Am. J. Physiol. (1992) [Pubmed]
  29. Involvement of thromboxane A2-thromboxane A2 receptor system of the hepatic sinusoid in pathogenesis of cold preservation/reperfusion injury in the rat liver graft. Ishiguro, S., Arii, S., Monden, K., Fujita, S., Nakamura, T., Niwano, M., Harada, T., Ushikubi, F., Narumiya, S., Imamura, M. Transplantation (1995) [Pubmed]
  30. Role of thromboxane A2 and prostacyclin in uninephrectomy-induced attenuation of ischemic renal injury. Kato, A., Hishida, A., Nakajima, T. Kidney Int. (1995) [Pubmed]
  31. Chronic thromboxane inhibition preserves function of rejecting rat renal allografts. Coffman, T.M., Ruiz, P., Sanfilippo, F., Klotman, P.E. Kidney Int. (1989) [Pubmed]
  32. Acute and chronic effects of thromboxane A2 inhibition on the renal hemodynamics in streptozotocin-induced diabetic rats. Uriu, K., Kaizu, K., Hashimoto, O., Komine, N., Etoh, S. Kidney Int. (1994) [Pubmed]
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