Clinical data | |
---|---|
ATC code |
|
Identifiers | |
| |
CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
KEGG | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C30H39FN4O4 |
Molar mass | 538.664 g·mol−1 |
3D model (JSmol) | |
| |
|
Ulimorelin (INN, USAN) (developmental code name TZP-101) is a drug with a modified cyclic peptide structure which acts as a selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a). [1] Unlike many related drugs, ulimorelin has little or no effect on growth hormone (GH) release in rats. [2] However, like ghrelin and other ghrelin agonists, ulimorelin does stimulate GH release with concomitant increases in insulin-like growth factor 1 (IGF-1) in humans. [3] It has been researched for enhancing gastrointestinal motility, especially in gastroparesis [4] and in aiding recovery of bowel function following gastrointestinal surgery, where opioid analgesic drugs used for post-operative pain relief may worsen existing constipation. [5] [6] [7] [8] While ulimorelin has been shown to increase both upper and lower gastrointestinal motility in rats, [8] and showed promising results initially in humans, [4] [6] it failed in pivotal clinical trials in post operative ileus. [7]
A common side effect of ghrelin is reduced blood pressure. Ulimorelin has been shown to inhibit vasoconstriction of rat arteries in vitro elicited by the α1-adrenoceptors agonists phenylephrine and methoxamine, and to increase artery tension at high concentrations. [9] Effects on blood pressure, however, were not observed in human clinical trials. [4] [7]
Ghrelin is a hormone primarily produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.
Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.
Motilin receptor is a G protein-coupled receptor that binds motilin. It was first cloned in 1999 by Merck Laboratories. and scientists have since been searching for compounds to modify its behavior.
Alvimopan is a drug which behaves as a peripherally acting μ-opioid receptor antagonist. With the limited ability to cross the blood–brain barrier and reach the μ-opioid receptors of the central nervous system, the clinically undesirable effects of centrally acting opioid antagonists are avoided without affecting the intended blockade of μ-opioid receptors in the gastrointestinal tract. It is currently only Food and Drug Administration approved for the treatment of postoperative ileus which it received in May 2008.
Mosapride is a gastroprokinetic agent that acts as a selective 5HT4 agonist. The major active metabolite of mosapride, known as M1, additionally acts as a 5HT3 antagonist, which accelerates gastric emptying throughout the whole of the gastrointestinal tract in humans, and is used for the treatment of gastritis, gastroesophageal reflux disease, functional dyspepsia and irritable bowel syndrome. It is recommended to be taken on an empty stomach (i.e. at least one hour before food or two hours after food).
Pancreatic polypeptide receptor 1, also known as Neuropeptide Y receptor type 4, is a protein that in humans is encoded by the PPYR1 gene.
A cholecystokinin receptor antagonist is a specific type of receptor antagonist which blocks the receptor sites for the peptide hormone cholecystokinin (CCK).
Itopride (INN; brand name Ganaton) is a prokinetic benzamide derivative. These drugs inhibit dopamine and acetylcholine esterase enzyme and have a gastrokinetic effect. Itopride is indicated for the treatment of functional dyspepsia and other gastrointestinal conditions. It is a combined D2 receptor antagonist and acetylcholinesterase inhibitor. Itopride is the dimethoxy analog of trimethobenzamide.
Tabimorelin (INN) is a drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, mimicking the effects of the endogenous peptide agonist ghrelin as a stimulator of growth hormone (GH) release. It was one of the first GH secretagogues developed and is largely a modified polypeptide, but it is nevertheless orally-active in vivo. Tabimorelin produced sustained increases in levels of GH and insulin-like growth factor 1 (IGF-1), along with smaller transient increases in levels of other hormones such as adrenocorticotropic hormone (ACTH), cortisol, and prolactin. However actual clinical effects in adults with growth hormone deficiency were limited, with only the most severely GH-deficient patients showing significant benefit, and tabimorelin was also found to act as a CYP3A4 inhibitor which could cause it to have undesirable interactions with other drugs.
Mitemcinal is a motilin agonist derived from the macrolide antibiotic, erythromycin. It was discovered in the labs of Chugai Pharma. Mitemcinal is orally administered and it is believed to have strong promotility effects. Promotility drugs relieve symptoms of reflux by speeding the clearance of acid from the oesophagus and stomach. The parent compound, erythromycin, has these characteristics, but mitemcinal lacks the antibiotic properties of erythromycin.
Glucagon-like peptide-1 (GLP-1) receptor agonists, also known as GLP-1 analogs, GLP-1DAs or incretin mimetics, are a class of anorectic drugs that reduce blood sugar and energy intake by activating the GLP-1 receptor. They mimic the actions of the endogenous incretin hormone GLP-1 that is released by the gut after eating.
A prokinetic agent is a type of small peptide drug which enhances gastrointestinal motility by increasing the frequency or strength of contractions, but without disrupting their rhythm. They are used to treat certain gastrointestinal symptoms, including abdominal discomfort, bloating, constipation, heart burn, nausea, and vomiting; and certain gastrointestinal disorders, including irritable bowel syndrome, gastritis, gastroparesis, and functional dyspepsia.
Velusetrag (INN, USAN; previously known as TD-5108) is an experimental drug candidate for the treatment of gastric neuromuscular disorders including gastroparesis, and lower gastrointestinal motility disorders including chronic idiopathic constipation and irritable bowel syndrome. It is a potent, selective, high efficacy 5-HT4 receptor serotonin agonist being developed by Theravance Biopharma and Alfa Wassermann. Velusetrag demonstrates less selectivity for other serotonin receptors, such as 5-HT2 and 5-HT3, to earlier generation 5-HT agonists like cisapride and tegaserod.
CJ-033466 is a drug which acts as a potent and selective 5-HT4 serotonin receptor partial agonist. In animal tests it stimulated gastrointestinal motility with 30 times the potency of cisapride, and with lower affinity for the hERG channel.
Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues of growth hormone (GH). They include agonists of the ghrelin/growth hormone secretagogue receptor (GHSR), such as ghrelin (lenomorelin), pralmorelin (GHRP-2), GHRP-6, examorelin (hexarelin), ipamorelin, and ibutamoren (MK-677), and agonists of the growth hormone-releasing hormone receptor (GHRHR), such as growth hormone-releasing hormone, CJC-1295, sermorelin, and tesamorelin.
Pralmorelin (INN), also known as pralmorelin hydrochloride (JAN) and pralmorelin dihydrochloride (USAN), as well as, notably, growth hormone-releasing peptide 2 (GHRP-2), is a growth hormone secretagogue (GHS) used as a diagnostic agent that is marketed by Kaken Pharmaceutical in Japan in a single-dose formulation for the assessment of growth hormone deficiency (GHD).
Anamorelin (INN), also known as anamorelin hydrochloride, is a non-peptide, orally-active, centrally-penetrant, selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) with appetite-enhancing and anabolic effects which is under development by Helsinn Healthcare SA for the treatment of cancer cachexia and anorexia.
Relamorelin is a synthetic peptide, centrally penetrant, selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) which is under development by Allergan pharmaceuticals for the treatment of diabetic gastroparesis, chronic idiopathic constipation, and anorexia nervosa. It is a pentapeptide and an analogue of ghrelin with improved potency and pharmacokinetics. In humans, relamorelin produces increases in plasma growth hormone, prolactin, and cortisol levels, and, like other GHSR agonists, increases appetite. As of June 2015, relamorelin is in phase II clinical trials for diabetic gastroparesis and constipation. The United States Food and Drug Administration (FDA) has granted Fast Track designation to relamorelin for diabetic gastroparesis. The development of the drug is uncertain as the most recent mention of it was in a 2019 SEC filing from the drug manufacturer lists the drug's expected launch year as 2024, but not in subsequent filings or press releases.
Ipamorelin (INN) (developmental code name NNC 26-0161) is a peptide selective agonist of the ghrelin/growth hormone secretagogue receptor (GHS) and a growth hormone secretagogue. It is a pentapeptide with the amino acid sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 that was derived from GHRP-1.
Examorelin (INN) (developmental code names EP-23905, MF-6003), also known as hexarelin, is a potent, synthetic, peptidic, orally-active, centrally-penetrant, and highly selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and a growth hormone secretagogue which was developed by Mediolanum Farmaceutici. It is a hexapeptide with the amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 which was derived from GHRP-6. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the ghrelin receptor.