Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C27H25N9O6S.2Na |
| Molecular Weight | 649.589 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].[Na+].COC1=C(OC2=C([N-]S(=O)(=O)C3=NC=C(C=C3)C(C)C)N=C(N=C2OCCO)C4=CC(=NC=C4)C5=NN=N[N-]5)C=CC=C1
InChI
InChIKey=LJEMFZYMXONDDJ-UHFFFAOYSA-N
InChI=1S/C27H25N9O6S.2Na/c1-16(2)18-8-9-22(29-15-18)43(38,39)34-26-23(42-21-7-5-4-6-20(21)40-3)27(41-13-12-37)31-24(30-26)17-10-11-28-19(14-17)25-32-35-36-33-25;;/h4-11,14-16,37H,12-13H2,1-3H3;;/q-2;2*+1
| Molecular Formula | C27H26N9O6S |
| Molecular Weight | 604.617 |
| Charge | -1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | Na |
| Molecular Weight | 22.9898 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15055997 | https://clinicaltrials.gov/ct2/show/NCT00524433 | https://www.ncbi.nlm.nih.gov/pubmed/14632537 | https://clinicaltrials.gov/ct2/show/NCT01077297 | https://www.ncbi.nlm.nih.gov/pubmed/22474738
Curator's Comment: The description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/15055997 | https://clinicaltrials.gov/ct2/show/NCT00524433 | https://www.ncbi.nlm.nih.gov/pubmed/14632537 | https://clinicaltrials.gov/ct2/show/NCT01077297 | https://www.ncbi.nlm.nih.gov/pubmed/22474738
Tezosentan (Veletri; Ro 61–0612) is a dual endothelin receptor antagonist that has been shown to improve cardiac output, decrease pulmonary capillary wedge pressure, and reduce pulmonary and systemic vascular resistance in initial clinical studies in acutely decompensated heart failure. Tezosentan is a water-soluble ET-1 receptor antagonist with high affinity to both ETA and ETB receptors but greater potency for the ETA receptor subtype. Clinical studies demonstrated mixed results for Tezosentan regarding its efficacy and tolerability in the management of decompensated heart failure. The side effects of Tezosentan include a headache, nausea, and hypotension.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| In vivo and in vitro disposition profile of tezosentan, an intravenous dual endothelin receptor antagonist, in humans. | 2003 Apr |
|
| Tezosentan in the treatment of acute heart failure. | 2003 Dec |
|
| Haemodynamic effects of endothelin receptor antagonist, tezosentan, in tumour necrosis factor-alpha treated anaesthetized rats. | 2003 Feb |
|
| Tezosentan in patients with acute heart failure and acute coronary syndromes: design of the fourth Randomized Intravenous Tezosentan Study (RITZ-4). | 2003 Feb |
|
| ETA and ETB receptor function in pancreatitis-associated microcirculatory failure, inflammation, and parenchymal injury. | 2003 Jul |
|
| Determination of tezosentan, a parenteral endothelin receptor antagonist, in human plasma by liquid chromatography-tandem mass spectrometry. | 2003 Jul 25 |
|
| Effect of severe renal impairment on the pharmacokinetics and tolerability of the parenteral endothelin antagonist tezosentan. | 2003 Jun |
|
| Current status of endothelin blockade for the treatment of cardiovascular and pulmonary vascular disease. | 2003 Mar |
|
| The neurohormonal paradigm: have we gone too far? | 2003 May 7 |
|
| Tezosentan in patients with acute heart failure and acute coronary syndromes: results of the Randomized Intravenous TeZosentan Study (RITZ-4). | 2003 May 7 |
|
| Effects of the endothelin-1 receptor antagonist tezosentan on renal blood flow and diuresis during prolonged increased intra-abdominal pressure. | 2003 Nov |
|
| Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats. | 2004 Dec |
|
| Tezosentan counteracts endotoxin-induced pulmonary edema and improves gas exchange. | 2004 Jun |
|
| Usefulness of an elevated troponin-I in predicting clinical events in patients admitted with acute heart failure and acute coronary syndrome (from the RITZ-4 trial). | 2004 Jun 1 |
|
| Novel endothelin receptor antagonist attenuates endotoxin-induced lung injury in sheep. | 2004 Mar |
|
| Differentiated and dose-related cardiovascular effects of a dual endothelin receptor antagonist in endotoxin shock. | 2004 May |
|
| Tezosentan reduces the microvascular filtration coefficient in isolated lungs from rats subjected to cecum ligation and puncture. | 2005 |
|
| Role of endothelin in alpha-adrenoceptor coronary vasoconstriction. | 2005 Apr |
|
| Renal blood flow in sepsis. | 2005 Aug |
|
| Clinical trials update from the American College of Cardiology meeting: CARE-HF and the remission of heart failure, Women's Health Study, TNT, COMPASS-HF, VERITAS, CANPAP, PEECH and PREMIER. | 2005 Aug |
|
| Echocardiographic ejection fraction in patients with acute heart failure: correlations with hemodynamic, clinical, and neurohormonal measures and short-term outcome. | 2005 Aug |
|
| Combination pharmacologic therapies for heart failure: what next after angiotensin-converting enzyme inhibitors and beta-blockers? | 2005 Aug |
|
| Tezosentan in the management of decompensated heart failure. | 2005 Jan-Feb |
|
| Tezosentan in patients with acute heart failure: design of the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Study (VERITAS). | 2005 Jul |
|
| Endothelin antagonists: new bullets against lung injury? | 2005 Jun |
|
| Tezosentan-induced attenuation of lung injury in endotoxemic sheep is associated with reduced activation of protein kinase C. | 2005 Jun |
|
| Effects of a dual endothelin-1 receptor antagonist on airway obstruction and acute lung injury in sheep following smoke inhalation and burn injury. | 2005 Mar |
|
| Carbon monoxide, but not endothelin-1, plays a major role for the hepatic microcirculation in a murine model of early systemic inflammation. | 2005 Oct |
|
| Endothelin-1 causes systemic vasodilatation in anaesthetised turtles (Trachemys scripta) through activation of ETB-receptors. | 2005 Oct |
|
| Nitric oxide blunts the endothelin-mediated pulmonary vasoconstriction in exercising swine. | 2005 Oct 15 |
|
| Pharmacology of new agents for acute heart failure syndromes. | 2005 Sep 19 |
|
| Overview of randomized clinical trials in acute heart failure syndromes. | 2005 Sep 19 |
|
| Year in review 2005: Critical Care--respirology: mechanical ventilation, infection, monitoring, and education. | 2006 |
|
| Medical and ventilatory treatment of acute heart failure: new insights. | 2006 |
|
| Effects of endothelin antagonist tezosentan on orthodontic tooth movement in rats. | 2006 Apr |
|
| Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects. | 2006 Apr |
|
| Endothelin-2 in ovarian follicle rupture. | 2006 Apr |
|
| Newer approaches to the pharmacological management of heart failure. | 2006 Feb |
|
| Tezosentan decreases pulmonary artery pressure and improves survival rate in an animal model of meconium aspiration. | 2006 Jan |
|
| Nebulized therapies for childhood pulmonary hypertension: an in vitro model. | 2006 Jul |
|
| Role of endothelin receptor activation in secondary pulmonary hypertension in awake swine after myocardial infarction. | 2006 Jul 15 |
|
| Endothelin receptors in light-induced retinal degeneration. | 2006 Jun |
|
| Effects of endothelin receptor antagonism on acute lung injury induced by chlorine gas. | 2006 Jun |
|
| Endothelin receptor antagonists. | 2006 Jun |
|
| The role of indomethacin and tezosentan on renal effects induced by Bothrops moojeni Lys49 myotoxin I. | 2006 Jun 15 |
|
| Optimizing outcomes in the patient with acute decompensated heart failure. | 2006 Mar |
|
| The role of endothelin-1 in hyperoxia-induced lung injury in mice. | 2006 Mar 27 |
|
| [Medical and ventilatory treatment of acute heart failure]. | 2006 Mar 9 |
|
| Nitric oxide-endothelin-1 interactions after surgically induced acute increases in pulmonary blood flow in intact lambs. | 2006 May |
|
| NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine. | 2006 Nov |
Patents
Sample Use Guides
single infusion of tezosentan 5mg/h over 30 min corresponding to 2.5 mg
Route of Administration:
Intravenous
Aortic valves were obtained from 16 patients at the time of aortic valve replacement surgery. After surgical removal, each valve was divided approximately into 15 pieces. Valve pieces (4 mm diameter) of normal and sclerotic aortic valves were cultured in αMEM (Gibco, Paisley, UK), supplemented with 10% heat-inactivated fetal bovine serum (FBS; Autogen Bioclear, Wiltshire, UK), 20 mM HEPES (Gibco) 100 U/ml penicillin, 0.1 mg/ml streptomycin (Gibco) and 2 mM L-glutamine (Gibco) at 37°C in 5% CO2 and 95% air. For the measurement of radioactivity in cell culture experiments, valve pieces from two normal patients (resulting in 30 valve pieces) as well as six stenotic patients (resulting in 90 valve pieces) were inserted into the 24-well plates, the medium was changed, and the test drugs (125I-ET-1, 10 nmol/l; ET-1, 100 µmol/l; tezosentan, 10 nmol/l) were added on the second day of culture. After 20 min and 3 h of incubation, the valves were washed three times with DPBS (BioWhittaker, Lonza, Belgium). Radioactivity was measured using a Wallac Multigamma counter (Wallac, Turku, Finland) and results were expressed as counts per minute.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 04:53:37 GMT 2023
by
admin
on
Sat Dec 16 04:53:37 GMT 2023
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| Record UNII |
2Q53CXJ1D6
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| Record Status |
Validated (UNII)
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| Record Version |
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