![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 290, Issue 2, 840-846, August 1999
Actelion Ltd., Innovation Center, Allschwil, Switzerland (M.C.,
H.R., J.-P.C., P.H.); and Hoffmann-La Roche Ltd., Basel, Switzerland
(V.B., B.M.L., P.C., S.R.)
Tezosentan (Ro 61-0612) [5-isopropyl-pyridine-2-sulfonic acid
6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide] is a new endothelin (ET) receptor antagonist specifically designed for
parenteral use. Tezosentan competitively antagonizes the specific binding of 125I-labeled ET-1 and of the selective
ETB receptor ligands 125I-labeled ET-3 and
125I-labeled sarafotoxin S6c on cells and tissues carrying
ETA and ETB receptors, with inhibitory
constants in the nanomolar range, and has high water solubility.
Tezosentan exhibits high functional inhibitory potency for inhibiting
contraction induced by ET-1 on isolated rat aorta (ETA
receptors; pA2 = 9.5) and by sarafotoxin S6c on rat
trachea (ETB receptors; pA2 = 7.7). In
vivo, tezosentan inhibits the pressor effect of big ET-1 in pithed rats
and increases ET-1 plasma concentrations in conscious rats in a
dose-dependent fashion. In spontaneously hypertensive rats, i.v.
injection of tezosentan has acute hemodynamic effects and decreases
blood pressure. Tezosentan is also able to prevent the acute renal
failure that complicates rhabdomyolysis in a rat model of myoglobinuric
nephropathy. Finally, tezosentan exhibits an apparent elimination
half-life of less than 1 h in rabbits and primates and of 2 h
in rats. In conclusion, tezosentan, a potent mixed ET receptor
antagonist with a short half-life, may offer a novel medical approach
for the i.v. treatment of acute pathological conditions.
This article has been cited by other articles:
|
|
 |
|
  J. Dingemanse, A. Halabi, and P. L. M. van Giersbergen Influence of Liver Cirrhosis on the Pharmacokinetics, Pharmacodynamics, and Safety of Tezosentan J. Clin. Pharmacol., April 1, 2009; 49(4): 455 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iglarz, C. Binkert, K. Morrison, W. Fischli, J. Gatfield, A. Treiber, T. Weller, M. H. Bolli, C. Boss, S. Buchmann, et al. Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 736 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-H. Rolland, P. de Lagausie, E. Stathopoulos, O. Lepretre, G. Viudes, G. Gorincour, G. Hery, C. de Magnee, O. Paut, and J.-M. Guys Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary arteries of preterm lambs with pulmonary vascular dysfunction Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2231 - H2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Iribarne, L. Ogawa, V. Torbidoni, C. M. Dodds, R. A. Dodds, and A. M. Suburo Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice Am. J. Pathol., April 1, 2008; 172(4): 1030 - 1042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Konrad, M. Haney, G. Johansson, M. Wanecek, E. Weitzberg, and A. Oldner Cardiac effects of endothelin receptor antagonism in endotoxemic pigs Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H988 - H996. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. C. Tsang, W. J. E. Lamm, B. Neradilek, N. L. Polissar, and M. P. Hlastala Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism J Appl Physiol, February 1, 2007; 102(2): 762 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N F Kelland and D J Webb Clinical trials of endothelin antagonists in heart failure: publication is good for the public health Heart, January 1, 2007; 93(1): 2 - 4. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Houweling, D. Merkus, O. Sorop, F. Boomsma, and D. J. Duncker Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction J. Physiol., July 15, 2006; 574(2): 615 - 626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Battistini, N. Berthiaume, N. F. Kelland, D. J. Webb, and D. E. Kohan Profile of Past and Current Clinical Trials Involving Endothelin Receptor Antagonists: The Novel "-Sentan" Class of Drug. Experimental Biology and Medicine, June 1, 2006; 231(6): 653 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Torbidoni, M. Iribarne, and A. M. Suburo Endothelin receptors in light-induced retinal degeneration. Experimental Biology and Medicine, June 1, 2006; 231(6): 1095 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ko, M. C. Gieske, L. Al-Alem, Y. Hahn, W. Su, M. C. Gong, M. Iglarz, and Y. Koo Endothelin-2 in Ovarian Follicle Rupture Endocrinology, April 1, 2006; 147(4): 1770 - 1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Skovgaard, D. E. Warren, D. C. Jackson, and T. Wang Endothelin-1 causes systemic vasodilatation in anaesthetised turtles (Trachemys scripta) through activation of ETB-receptors J. Exp. Biol., October 1, 2005; 208(19): 3739 - 3746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Merkus, B. Houweling, A. H. van den Meiracker, F. Boomsma, and D. J. Duncker Contribution of endothelin to coronary vasomotor tone is abolished after myocardial infarction Am J Physiol Heart Circ Physiol, February 1, 2005; 288(2): H871 - H880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W Urbanowicz, P Sogni, R Moreau, K A Tazi, E Barriere, O Poirel, A Martin, M C Guimont, D Cazals-Hatem, and D Lebrec Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats Gut, December 1, 2004; 53(12): 1844 - 1849. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Picker, L. A. Schwarte, H. J. Roth, J. Greve, and T. W. L. Scheeren Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs Br. J. Anaesth., January 1, 2004; 92(1): 102 - 108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M Tovar and J. G Gums Tezosentan in the Treatment of Acute Heart Failure Ann. Pharmacother., December 1, 2003; 37(12): 1877 - 1883. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Merkus, B. Houweling, A. Mirza, F. Boomsma, A. H van den Meiracker, and D. J Duncker Contribution of endothelin and its receptors to the regulation of vascular tone during exercise is different in the systemic, coronary and pulmonary circulation Cardiovasc Res, September 1, 2003; 59(3): 745 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Torre-Amione, J. B. Young, W. S. Colucci, B. S. Lewis, C. Pratt, G. Cotter, K. Stangl, U. Elkayam, J. R. Teerlink, A. Frey, et al. Hemodynamic and clinical effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients hospitalized for acute decompensated heart failure J. Am. Coll. Cardiol., July 2, 2003; 42(1): 140 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Plusczyk, B. Witzel, M. D. Menger, and M. Schilling ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury Am J Physiol Gastrointest Liver Physiol, June 9, 2003; 285(1): G145 - G153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. O'Connor, W. A. Gattis, K. F. Adams Jr, V. Hasselblad, B. Chandler, A. Frey, I. Kobrin, M. Rainisio, M. R. Shah, J. Teerlink, et al. Tezosentan in patients with acuteheart failure and acute coronary syndromes: Results of the randomized intravenous tezosentan study (ritz-4) J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1452 - 1457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F Markos, B A Hennessy, M Fitzpatrick, J O'Sullivan, and H M Snow The effect of tezosentan, a non-selective endothelin receptor antagonist, on shear stress-induced changes in arterial diameter of the anaesthetized dog J. Physiol., November 1, 2002; 544(3): 913 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Davenport International Union of Pharmacology. XXIX. Update on Endothelin Receptor Nomenclature Pharmacol. Rev., June 1, 2002; 54(2): 219 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V Agapitov and W. G Haynes Role of endothelin in cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 1 - 15. [Abstract] [PDF]
|
|
|
|
|
|
S.-S. Ding, C. Qiu, P. Hess, J.-F. Xi, J.-P. Clozel, and M. Clozel Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure Cardiovasc Res, March 1, 2002; 53(4): 963 - 970. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Clozel, C. Qiu, C.-S. Qiu, P. Hess, and J.-P. Clozel Short-term endothelin receptor blockade with tezosentan has both immediate and long-term beneficial effects in rats with myocardial infarction J. Am. Coll. Cardiol., January 2, 2002; 39(1): 142 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Picker, A. W. Schindler, and T. W. L. Scheeren Endogenous Endothelin and Vasopressin Support Blood Pressure During Epidural Anesthesia in Conscious Dogs Anesth. Analg., December 1, 2001; 93(6): 1580 - 1586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Torre-Amione, J.-B. Durand, S. Nagueh, M. T. Vooletich, I. Kobrin, and C. Pratt A Pilot Safety Trial of Prolonged (48 h) Infusion of the Dual Endothelin-Receptor Antagonist Tezosentan in Patients With Advanced Heart Failure Chest, August 1, 2001; 120(2): 460 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Torre-Amione, J. B. Young, J.-B. Durand, B. Bozkurt, D. L. Mann, I. Kobrin, and C. M. Pratt Hemodynamic Effects of Tezosentan, an Intravenous Dual Endothelin Receptor Antagonist, in Patients With Class III to IV Congestive Heart Failure Circulation, February 20, 2001; 103(7): 973 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takamura, R. Parent, P. Cernacek, and M. Lavallee Influence of dual ETA/ETB-receptor blockade on coronary responses to treadmill exercise in dogs J Appl Physiol, November 1, 2000; 89(5): 2041 - 2048. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
