ERAsRepresent a new promising tPulmonaryA192621MacitentanInhibitorsSelectivePotentDeleterious effectsBlockadePathwaysDrugDrugsBosentanPulmonaryVasoconstrictionProstacyclinEndothelial cellsSelective antagonistNitric oxideAmbrisentanProtein-coupled receptorsVascular smooth musclAngiotensinPeptideEndotheliumTherapeuticClinicalProteinsTransientCardiacCardiovascularBindExperimentalAcutePatientsTreatmentReferencesActivityBlocksTypeDevelopment
ERAs1
- Endothelin receptor antagonists (ERAs) are an important part of PAH therapy, with two ERAs currently approved for the treatment of PAH and a novel ERA that has recently been investigated in a Phase III clinical trial. (nih.gov)
Represent a new promising t1
- Our findings support the hypothesis that ETB antagonists represent a new promising therapeutic strategy for the treatment of high grade gliomas. (unipv.it)
Pulmonary4
- Three pathways have been identified in the pathogenesis of pulmonary arterial hypertension (PAH): the endothelin (ET), nitric oxide (NO) and prostacyclin pathways. (nih.gov)
- Endothelin receptor antagonists bind endothelin 1 receptors, causing a decrease in pulmonary arterial pressure through decreases in PVR. (medscape.com)
- Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. (globalrph.com)
- OPSUMIT® is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. (globalrph.com)
A1926213
- selective ETB receptor antagonists (BQ-788 and A192621) which affect endothelin B receptors are used in research but have not yet reached the clinical trial stage. (wikipedia.org)
- In this study we have investigated the effects of two structurally unrelated ETB receptor antagonists, BQ788 and A192621, on cell survival, proliferation and apoptosis in 1321-N1, U87 and IPDDCA2 glioma cell lines. (unipv.it)
- BQ788 and A192621 reduced glioma cells viability and proliferation assessed by BrdU incorporation and cell cycle analysis by flow cytometry, while in contrast the ETA receptor antagonist BQ123 had no effect on cell survival. (unipv.it)
Macitentan3
- OPSUMIT (macitentan) is an endothelin receptor antagonist. (globalrph.com)
- Macitentan is an endothelin receptor antagonist that prevents the binding of ET-1 to both ETA and ETB receptors. (globalrph.com)
- One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. (globalrph.com)
Inhibitors1
- For management of heart failure with reduced ejection fraction (HFrEF), medication classes consist of diuretics, angiotensin-receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, and beta-blockers. (medscape.com)
Selective2
- In the experimental Goto Kakizaki rat, a model of Type II diabetes, hyperglycaemia and reduced glucose clearance is associated with elevated plasma endothelin (ET)-1 levels and selective decreases in nitric oxide synthase in circular muscle, longitudinal muscle and neuronal elements of the gastrointestinal tract. (portlandpress.com)
- Long-term treatment with a selective ET A-type receptor antagonist, markedly reduced hyperglycaemia and restored plasma glucose clearance rates towards normal. (portlandpress.com)
Potent2
- Endothelin 1 is a potent endogenous vasoconstrictor that causes vascular smooth muscle hyperplasia in addition to direct vasoconstrictor effects. (medscape.com)
- A synthetic opioid analgesic that is primarily a mu receptor agonist, fentanyl is 50-100 times more potent than morphine. (medscape.com)
Deleterious effects2
- The ET system is well established as a key player in the pathophysiology of PAH, with deleterious effects mediated by both the ETA and ETB receptors. (nih.gov)
- Endothelin (ET)-1 and its receptors (ETA and ETB) mediate a variety of deleterious effects, such as vasoconstriction, fibrosis, proliferation, hypertrophy, and inflammation. (globalrph.com)
Blockade3
- The results indicate that beneficial effects of ETA receptor blockade on gastrointestinal function may result from an improvement in insulin sensitivity with concomitant reduction of the severity of hyperglycaemia. (portlandpress.com)
- ETA receptor blockade may represent a new therapeutic principle for improving glucose tolerance in Type II diabetes and could be beneficial in alleviating or preventing hyperglycaemia-related secondary complications in this condition. (portlandpress.com)
- The blockade of vasopressin receptors with tolvaptan continues to make appearances as a potential therapy in multiple arenas. (medscape.com)
Pathways3
- Furthermore, treatment with ETB antagonists downregulates ERK- and p38MAPK-dependent pathways but does not affect VEGF mRNA levels. (unipv.it)
- An opioid agonist/antagonist, nalbuphine stimulates kappa opioid receptor in the CNS, which causes inhibition of ascending pain pathways. (medscape.com)
- Codeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering perception and response to pain. (medscape.com)
Drug1
- An endothelin receptor antagonist (ERA) is a drug that blocks endothelin receptors. (wikipedia.org)
Drugs1
- The proliferative and antiapoptotic actions of endothelin (ET)-1 in cancer cells have been documented and ET receptor antagonists have been exploited as potential anticancer drugs. (unipv.it)
Bosentan4
- Since 2002, the dual endothelin receptor antagonist (ERA) bosentan has been avail- able for the management of PAH. (medscape.com)
- Bosentan is a dual endothelin A and B receptor antagonist for treatment of pulmonary arterial hypertension. (medscape.com)
- Three endothelin receptor antagonists are currently approved and in use in the United States: bosentan (2001: Tracleer), ambrisentan (2007: Letairis) and macitentan (2013: Opsumit). (nih.gov)
- While all endothelin receptor antagonists have been associated with occasional transient serum enzyme elevations during therapy, only bosentan and sitaxentan have been clearly linked to instances of clinically apparent, acute liver injury. (nih.gov)
Pulmonary16
- Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. (medscape.com)
- Ambrisentan is an endothelin receptor antagonist indicated for pulmonary arterial hypertension in patients with World Health Organization (WHO) class II or III symptoms. (medscape.com)
- Endothelin receptors are relatively enriched in pulmonary vasculature and their inibition results in a decrease in pulmonary vascular pressure. (nih.gov)
- In patients with pulmonary arterial hypertension, (PAH) the endothelin receptor antagonists have been shown to improve exercise tolerance and slow progression of disease. (nih.gov)
- The use of endothelin receptor antagonists in pulmonary arterial hypertension (PAH) is based upon the proposed pathogenesis of this disease, which is marked by enhanced synthesis of ET-1 and progressive proliferation and hypertrophy of smooth muscle cells in the pulmonary vasculature. (nih.gov)
- In several randomized controlled trials, endothelin receptor antagonists were shown to decrease pulmonary vascular pressure and improve exercise tolerance and symptoms in patients with PAH. (nih.gov)
- CH, however, induces pulmonary hypertension, right ventricle (RV) hypertrophy, vascular remodelling [ 14 ] and increased plasma levels of endothelin (ET)-1 in the guinea pig [ 15 ]. (ersjournals.com)
- Controlled exposures of animals and humans to particulate matter (PM) or ozone air pollution cause an increase in plasma levels of endothelin-1, a potent vasoconstrictor that regulates pulmonary arterial pressure. (nih.gov)
- The primary objective of this field study was to determine whether Mexico City children, who are chronically exposed to levels of PM and O 3 that exceed the United States air quality standards, have elevated plasma endothelin-1 levels and pulmonary arterial pressures. (nih.gov)
- Plasma endothelin-1 concentrations were determined by immunoassay, and pulmonary arterial pressures were measured by Doppler echocardiography. (nih.gov)
- Chronic exposure of children to PM 2.5 is associated with increased levels of circulating endothelin-1 and elevated mean pulmonary arterial pressure. (nih.gov)
- Selexipag is an oral selective prostacyclin-receptor agonist that was approved for use in patients with World Health Organisation (WHO) functional class II-III pulmonary arterial hypertension (PAH). (bjcardio.co.uk)
- Treatment with individualised doses of selexipag resulted in significant reductions in the composite end point of death or a complication related to PAH in the phase III GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) study. (bjcardio.co.uk)
- Current therapy targets the nitric oxide, endothelin and prostacyclin pathways to promote pulmonary vasodilatation and reduce right ventricular afterload. (bjcardio.co.uk)
- In the GRIPHON (Prostacyclin [PGI2] Receptor Agonist In Pulmonary Arterial Hypertension) trial the optimum dose of selexipag for maximum therapeutic benefit frequently differed between individual patients. (bjcardio.co.uk)
- Homology modeling, molecular dynamics and virtual screening of endothelin-A receptor for the treatment of pulmonary arterial hypertension. (nih.gov)
Vasoconstriction4
- ET-1 acts by engagement of cell surface receptors that result in activation of intracellular pathways leading to vasoconstriction and proliferation of smooth muscle cells. (nih.gov)
- Among them, endothelin A receptors are mainly located on vascular smooth muscle cells and mediate vasoconstriction. (immune-system-research.com)
- ET A receptors on the endothelial cells stimulate vasoconstriction and proliferation while the ET B receptors are thought to stimulate the release of NO and PGI 2 , leading to vasodilation and counteracting the effects of ET A and ultimately ET-1. (uspharmacist.com)
- This gene encodes the receptor for endothelin-1, a peptide that plays a role in potent and long-lasting vasoconstriction. (nih.gov)
Prostacyclin3
- 7 Current drug therapies and research are centered on treating and correcting dysfunctional pathways, which include prostacyclin (PGI 2 ), endothelin-1 (ET-1), and nitric oxide (NO) in vascular smooth muscle cells. (uspharmacist.com)
- 1,2 Selexipag is an oral selective prostacyclin-receptor agonist that is used in the treatment of PAH. (bjcardio.co.uk)
- It is postulated that this relates to variations in prostacyclin (IP) receptor expression and density. (bjcardio.co.uk)
Endothelial cells3
- The ETA receptor is found predominantly on smooth muscle cells, whereas the ETB receptor is present on both smooth muscle and vascular endothelial cells. (nih.gov)
- Endothelin is a vasoconstrictor peptide composed of 21 amino acids that is mainly produced in endothelial cells and plays a key role in vascular homeostasis. (immune-system-research.com)
- Endothelin A receptors contribute to senescence of brain microvascular endothelial cells. (nih.gov)
Selective antagonist3
- Since it has been shown that the contractile effects of endothelins in the aorta are mediated by the endothelin ET A receptor whereas the endothelium-dependent relaxation and the ileal relaxation are mediated by the endothelin ET B receptor, it is suggested that RES-701-1 is a selective antagonist against the endothelin ET B receptor. (unair.ac.id)
- Since it has been shown that the contractile effects of endothelins in the aorta are mediated by the endothelin ETA receptor whereas the endothelium-dependent relaxation and the ileal relaxation are mediated by the endothelin ETB receptor, it is suggested that RES-701-1 is a selective antagonist against the endothelin ETB receptor. (unair.ac.id)
- The positive inotropic effect and the hydrolysis of phosphoinositide induced by endothelin-3 in rabbit ventricular myocardium: inhibition by a selective antagonist of ET(A) receptors, FR139317. (aspetjournals.org)
Nitric oxide1
- Regulation of cardiac nitric oxide signalling by nuclear β-adrenergic and endothelin receptors. (icm-mhi.org)
Ambrisentan1
- Ambrisentan inhibits vessel constriction and elevation of blood pressure by competitively binding to endothelin-1 receptors ETA and ETB in endothelium and vascular smooth muscle. (medscape.com)
Protein-coupled receptors1
- Endothelin acts by activating two G protein-coupled receptors , the endothelin A and endothelin B receptors. (immune-system-research.com)
Vascular smooth muscl1
- These agents bind to endothelin receptors present in endothelium and vascular smooth muscle cells. (medscape.com)
Angiotensin2
- Sparsentan (RE-021) is a highly potent dual angiotensin II and endothelin A receptor antagonist with K i values of 0.8 and 9.3 nM, respectively. (immune-system-research.com)
- In conclusion, Sparsentan (RE-021) is a highly selective dual antagonist of angiotensin II and endothelin A receptors and can be used in the study of hypertensive disorders, etc. (immune-system-research.com)
Peptide2
- The endothelin receptor antagonists inhibit the binding of endothelin, a vasoconstrictive peptide, to its receptors on smooth muscle cells which results in vasodilation. (nih.gov)
- Endothelin-1 (ET-1) is a 21 amino acid peptide that acts in a paracrine and autocrine fashion as a potent vasoconstrictor. (nih.gov)
Endothelium3
- In isolated rat aorta without endothelium, 10 μM RES-701-1 did not affect the resting tone, nor did it attenuate the contractions induced by endothelin-1, endothelin-3 or norepinephrine. (unair.ac.id)
- In the aorta with endothelium, 3 μM RES-701-1 shifted the concentration-response curves for the contractile effects of endothelin-1 and endothelin-3 to the left. (unair.ac.id)
- In the norepinephrine-stimulated aorta, endothelium-dependent relaxation induced by endothelin-3 was antagonized by 0.3-10 μM RES-701-1 in a concentration-dependent manner. (unair.ac.id)
Therapeutic1
- Summary of the ASPET-sponsored Colloquium: Alpha-2 adrenergic receptors: structure, function, and therapeutic implications, October 25-27, 1995. (aspetjournals.org)
Clinical2
- selective ETB receptor antagonists (BQ-788 and A192621) which affect endothelin B receptors are used in research but have not yet reached the clinical trial stage. (wikipedia.org)
- We outline the current understanding of not only the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH but also the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH. (medscape.com)
Proteins1
- This receptor associates with guanine-nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. (nih.gov)
Transient2
- The endothelin receptor antagonists have been associated with a low, but appreciable rate of serum enzyme elevations during therapy that are generally transient and mild, but can cause mild symptoms and require dose modification or discontinuation. (nih.gov)
- In the guinea pig ileum stimulated by carbachol, endothelin-3 induced a transient relaxation followed by sustained relaxation. (unair.ac.id)
Cardiac1
- CPVT is caused by mutations in the cardiac ryanodine receptor (RyR2) or in the sarcoplasmic. (researchgate.net)
Cardiovascular1
- Endothelin A receptors are selective for endothelin 1, which contributes to vascular dysfunction associated with cardiovascular disease, especially atherosclerosis and hypertension . (immune-system-research.com)
Bind1
- Compounds and drugs that bind to and inhibit or block the activation of ENDOTHELIN RECECPTORS. (bvsalud.org)
Experimental1
- Recent investigations demonstrated that the thromboxane (TX) A 2 receptor (TP) antagonist NTP42 attenuates experimental PAH across key hemodynamic parameters in the lungs and heart. (frontiersin.org)
Acute2
- Several endothelin receptor antagonists have been associated with rare, but potentially severe instances of clinically apparent, acute liver injury. (nih.gov)
- Coadministration of endothelin antagonists with sparsentan is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (eg, acute renal failure). (medscape.com)
Patients1
- The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension. (nih.gov)
Treatment1
- RECEPTORS) and is used in the treatment of metastatic NON-SMALL CELL LUNG CANCER. (nih.gov)
References1
- The three endothelin receptor antagonists are discussed separately with references appropriate for each agent. (nih.gov)
Activity1
- Endothelin-A receptor in gastric cancer and enhanced antitumor activity of trastuzumab in combination with the endothelin-A receptor antagonist ZD4054. (nih.gov)
Blocks1
- A Fab fragment of the chimeric monoclonal antibody 7E3 that binds to the glycoprotein IIb-IIIa receptor of human platelets, and blocks PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX, potently inhibiting PLATELET AGGREGATION. (nih.gov)
Type2
Development1
- A non-receptor tyrosine kinase that is essential for the development, maturation, and signaling of B-LYMPHOCYTES. (nih.gov)