Attenuation of opioid tolerance by ET B receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice

Gulati, Shruti; Briyal, Seema; Jones, S.; Bhalla, Shaifali; Gulati, Anil

doi:10.1016/j.heliyon.2017.e00317

Cited by 4 publications

(2 citation statements)

References 53 publications

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“…Possibly, this represents a new opioid-sparing approach for patients with chronic pain requiring opioid therapy or opioid addiction 557,558 and possibly requires ET B receptors. 559…”

Section: Neurological and Eye Diseases Painmentioning

confidence: 99%

Endothelin: 30 Years From Discovery to Therapy

2019

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Discovered in 1987 as a potent endothelial cell–derived vasoconstrictor peptide, endothelin-1 (ET-1), the predominant member of the endothelin peptide family, is now recognized as a multifunctional peptide with cytokine-like activity contributing to almost all aspects of physiology and cell function. More than 30 000 scientific articles on endothelin were published over the past 3 decades, leading to the development and subsequent regulatory approval of a new class of therapeutics—the endothelin receptor antagonists (ERAs). This article reviews the history of the discovery of endothelin and its role in genetics, physiology, and disease. Here, we summarize the main clinical trials using ERAs and discuss the role of endothelin in cardiovascular diseases such as arterial hypertension, preecclampsia, coronary atherosclerosis, myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) caused by spontaneous coronary artery dissection (SCAD), Takotsubo syndrome, and heart failure. We also discuss how endothelins contributes to diabetic kidney disease and focal segmental glomerulosclerosis, pulmonary arterial hypertension, as well as cancer, immune disorders, and allograft rejection (which all involve ET A autoantibodies), and neurological diseases. The application of ERAs, dual endothelin receptor/angiotensin receptor antagonists (DARAs), selective ET B agonists, novel biologics such as receptor-targeting antibodies, or immunization against ET A receptors holds the potential to slow the progression or even reverse chronic noncommunicable diseases. Future clinical studies will show whether targeting endothelin receptors can prevent or reduce disability from disease and improve clinical outcome, quality of life, and survival in patients.

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“…Possibly, this represents a new opioid-sparing approach for patients with chronic pain requiring opioid therapy or opioid addiction 557,558 and possibly requires ET B receptors. 559…”

Section: Neurological and Eye Diseases Painmentioning

confidence: 99%

Endothelin: 30 Years From Discovery to Therapy

2019

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“…Although the N-terminus incorporates an N-Succinyl modification to reduce metabolism by non-specific peptidases, plasma half-life is short (only a few minutes) and as a modified peptide it is not orally active and requires administration by injection. Despite this unpromising profile, this compound, known as PMZ-1620, is being explored in a number of diseases associated with the CNS in animal models and in clinical studies (Gulati 2016, Gulati et al 2017, Joshi et al 2016. The therapeutic strategy is to exploit the IRL-1620 induced vasodilatation and neuroprotection mediated by the ET B receptor.…”

Section: Et B Agonists: Irl1620 (Pmz-1620 Spi-1620) In Stroke Alzhementioning

confidence: 99%

New Drugs and Emerging Therapeutic Targets in the Endothelin Signaling Pathway and Prospects for Personalized Precision Medicine

Davenport

Kuc²,

Southan³

et al. 2018

Physiol Res

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During the last thirty years since the discovery of endothelin-1, the therapeutic strategy that has evolved in the clinic, mainly in the treatment of pulmonary arterial hypertension, is to block the action of the peptide either at the ETA subtype or both receptors using orally active small molecule antagonists. Recently, there has been a rapid expansion in research targeting ET receptors using chemical entities other than small molecules, particularly monoclonal antibody antagonists and selective peptide agonists and antagonists. While usually sacrificing oral bio-availability, these compounds have other therapeutic advantages with the potential to considerably expand drug targets in the endothelin pathway and extend treatment to other pathophysiological conditions. Where the small molecule approach has been retained, a novel strategy to combine two vasoconstrictor targets, the angiotensin AT1 receptor as well as the ETA receptor in the dual antagonist sparsentan has been developed. A second emerging strategy is to combine drugs that have two different targets, the ETA antagonist ambrisentan with the phosphodiesterase inhibitor tadalafil, to improve the treatment of pulmonary arterial hypertension. The solving of the crystal structure of the ETB receptor has the potential to identify allosteric binding sites for novel ligands. A further key advance is the experimental validation of a single nucleotide polymorphism that has genome wide significance in five vascular diseases and that significantly increases the amount of big endothelin-1 precursor in the plasma. This observation provides a rationale for testing this single nucleotide polymorphism to stratify patients for allocation to treatment with endothelin agents and highlights the potential to use personalized precision medicine in the endothelin field.

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Endogenous opiates and behavior: 2017

Bodnar

2020

Peptides

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Attenuation of opioid tolerance by ET B receptor agonist, IRL-1620, is independent of an accompanied decrease in nerve growth factor in mice

Cited by 4 publications

References 53 publications

Endothelin: 30 Years From Discovery to Therapy

Endothelin: 30 Years From Discovery to Therapy

New Drugs and Emerging Therapeutic Targets in the Endothelin Signaling Pathway and Prospects for Personalized Precision Medicine

Endogenous opiates and behavior: 2017

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