Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131

Ploeg, Lex Van der; Laken, Haley; Sharma, Shubh D.; Datta, Rakesh; Halem, Heather; Dong, Jesse Z.; Touvay, Caroline; Teillot, Marc; Noonan, Patrick K.; Tartaglia, Lou; Stoner, Liz; Henderson, Bart; Gottesdiener, Keith; Culler, Michael D.

doi:10.1016/j.lfs.2014.06.003

Cited by 49 publications

(48 citation statements)

References 57 publications

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“…Moreover, in a rat model of TNBS-induced GI inflammation the administration of a single dose of RM-131 (5 or 50 nmol/mouse) increased the rats' survival and reduced signs of macroscopic colonic inflammation, suggesting that RM-131 also mediates an anti-inflammatory response. 36 Translated into humans, in a randomized, double-blinded, placebo-controlled trial, RM-131 administered subcutaneously for 14 days at the dose of 100 µg/day significantly reduced the symptoms of constipation in females with CC who met the Rome III criteria. 37 RM-131 significantly enhanced bowel function by increasing the number of spontaneous bowel movements and accelerated GI and colonic transit.…”

Section: Relamorelinmentioning

confidence: 99%

“…It binds to the GRLN-R with approximately 3-fold higher affinity to ghrelin receptors than native ghrelin. 36,37 Moreover, RM-131 exerts improved stability, greater potency, and longer plasma half-life. 36,38 RM-131 may be used in the treatment of gastroparesis, since in gastroparesis RM-131 accelerates gastric emptying without causing severe adverse effects.…”

Section: Relamorelinmentioning

confidence: 99%

“…39 Considering the prokinetic properties of RM-131 on the upper GI tract, many studies put also an interest on its effect in the treatment of the lower GI motility disorders. A study by Van der Ploeg et al 36 showed that RM-131 reversed the reduction of gastric emptying and was up to 100-fold more potent than ghrelin or other ghrelin mimetics in rat models of POI and morphine-induced ileus. Besides its effect on gastric emptying, oral administration of RM-131 also enhanced GI transit in the proximal and middle part of the small intestine.…”

Section: Relamorelinmentioning

confidence: 99%

See 2 more Smart Citations

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

Mosińska

Zatorski

Storr³

et al. 2017

J Neurogastroenterol Motil

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There is an unmet need for effective pharmacological therapies for constipation, a symptom that significantly deteriorates patients' quality of life and impacts health care. Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor and has been shown to exert prokinetic effects on gastrointestinal (GI) motility via the vagus and pelvic nerves. The pharmacological potential of ghrelin is hampered by its short half-life. Ghrelin receptor (GRLN-R) agonists with enhanced pharmacokinetics were thus developed. Centrally penetrant GRLN-R agonists stimulate defecation and improve impaired lower GI transit in animals and humans. This review summarizes the current knowledge on relamorelin, a potent ghrelin mimetic, and other GRLN-R analogs which are in preclinical or clinical stages of development for the management of disorders with underlying GI hypomotility, like constipation.

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Section: Relamorelinmentioning

confidence: 99%

Section: Relamorelinmentioning

confidence: 99%

Section: Relamorelinmentioning

confidence: 99%

See 1 more Smart Citation

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

Mosińska

Zatorski

Storr³

et al. 2017

J Neurogastroenterol Motil

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show abstract

“…111 A third compound, relamorelin (also known as RM-131) is currently in phase II clinical trials and is being developed for treatment of diabetic gastroparesis and other gastrointestinal (GI) disorders. 112 The orexigenic and lipogenic effect of ghrelin provide a potential use of ghrelin antagonists or reverse agonists in the treatment of obesity. 113 However, studies in this area show conflicting results as ghrelin antagonist reduced bodyweight and food intake in some studies, 114,115 while it increased weight gain and food intake in another studies.…”

Section: Clinical Applications Of Ghrelin and Ghrelin Antagonistmentioning

confidence: 99%

Ghrelin – Physiological Functions and Regulation

Abdalla

2015

European Endocrinology

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Ghrelin is an orexigenic peptide predominantly secreted from the stomach and stimulates appetite and growth hormone (GH) release.Studies have provided evidence that ghrelin exercises a wide range of functions, including regulation of food intake and energy metabolism, modulation of cardiovascular function, stimulation of osteoblast proliferation and bone formation and stimulation of neurogenesis and myogenesis. In the gastrointestinal system, ghrelin affects multiple functions, including secretion of gastric acid, gastric motility and pancreatic protein output. Most of these functions have been attributed to the actions of acylated ghrelin. The balance among its secretion rate, degradation rate and clearance rate determines the circulating level of ghrelin. This review explains what ghrelin is, its physiological functions and the factors that influence its level. KeywordsGhrelin, food intake, obesity, lipolysis, ghrelin receptors, regulation Disclosure: Mona Mohamed Ibrahim Abdalla has no conflicts of interest to declare. Acknowledgement:A note of appreciation to Research Management Centre of MAHSA University, Malaysia for funding publication of this article.

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“…RM-131 is a novel pentapeptide ghrelin receptor agonist with 100-fold more potency than human ghrelin in reversing gastric ileus in animal [84]. In pre-clinical studies prior to acquisition of RM-131 by Rhythm Pharmaceuticals, RM-131 has been shown to cause a dose-dependent increase in food intake and weight gain (both fat and lean mass) with greater potency than human ghrelin [85].…”

Section: Current Clinical Trials Of Ghrelin Agonists In Gastroparesismentioning

confidence: 99%

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

Shin

2015

Curr Gastroenterol Rep

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There remains an unmet need for effective pharmacologic treatments for gastroparesis.Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101 initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131 was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

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Preclinical gastrointestinal prokinetic efficacy and endocrine effects of the ghrelin mimetic RM-131

Cited by 49 publications

References 57 publications

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

Ghrelin – Physiological Functions and Regulation

Therapeutic Applications of Ghrelin Agonists in the Treatment of Gastroparesis

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