Capromorelin

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Capromorelin
Capromorelin skeletal.svg
Clinical data
Trade names Entyce, Elura
Other namesCP-424,391
License data
Routes of
administration 		By mouth
ATCvet code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life 2.4 hours [2]
Identifiers
  • N-[(2R)-1-[(3aR)-2-methyl-3-oxo-3a-(phenylmethyl)-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-5-yl]-1-oxo-3-(phenylmethoxy)propan-2-yl]-2-amino-2-methylpropanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C28H35N5O4
Molar mass 505.619 g·mol−1
3D model (JSmol)
  • CC(C)(C(=O)N[C@H](COCC1=CC=CC=C1)C(=O)N2CCC3=NN(C(=O)[C@@]3(C2)CC4=CC=CC=C4)C)N
  • InChI=1S/C28H35N5O4/c1-27(2,29)25(35)30-22(18-37-17-21-12-8-5-9-13-21)24(34)33-15-14-23-28(19-33,26(36)32(3)31-23)16-20-10-6-4-7-11-20/h4-13,22H,14-19,29H2,1-3H3,(H,30,35)/t22-,28-/m1/s1 Yes check.svgY
  • Key:KVLLHLWBPNCVNR-SKCUWOTOSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Capromorelin, sold under the brand names, Entyce and Elura, is a medication used for the management of weight loss in cats and dogs. [3] [4] Capromorelin is a ghrelin receptor agonist known to increase appetite and weight gain. [1]

Contents

Capromorelin was developed by Pfizer. [5] [6]

Capromorelin was approved for veterinary use in the United States in May 2016. [7] It is the second drug approved for the management of weight loss in cats and the first drug approved specifically for the management of weight loss in cats with chronic kidney disease. [1]

Research

Capromorelin functions to stimulate the secretion of growth hormone and as a ghrelin mimetic which causes the body to secrete human growth hormone in a way usually seen at puberty and in young adulthood. Studies have shown the drug to directly raise insulin growth factor 1 (IGF-1) and growth hormone levels. [8]

In a one-year treatment trial (starting 1999) with 395 seniors between 65 and 84 years old, patients who received the drug gained an average of 3 lb (1.4 kg) in lean body mass in the first six months and also were better able to walk in a straight line in a test of balance, strength and coordination. After 12 months, patients receiving capromorelin also had an improved ability to climb stairs, however the results were not good enough to continue the trial for the 2nd planned year. [9]

As of 2017, capromorelin studies in humans had been discontinued. [10]

Veterinary uses

Capromorelin is indicated for the management of weight loss in cats and dogs. [1]

Related Research Articles

<span class="mw-page-title-main">Growth hormone</span> Peptide hormone that stimulates growth, cell reproduction and cell regeneration

Growth hormone (GH) or somatotropin, also known as human growth hormone in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in human development. GH also stimulates production of IGF-1 and increases the concentration of glucose and free fatty acids. It is a type of mitogen which is specific only to the receptors on certain types of cells. GH is a 191-amino acid, single-chain polypeptide that is synthesized, stored and secreted by somatotropic cells within the lateral wings of the anterior pituitary gland.

<span class="mw-page-title-main">Ghrelin</span> Peptide hormone involved in appetite regulation

Ghrelin is a hormone 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.

<span class="mw-page-title-main">Anti-obesity medication</span> Class of pharmacological agents

Anti-obesity medication or weight loss medications are pharmacological agents that reduce or control weight. These medications alter one of the fundamental processes of the human body, weight regulation, by altering either appetite, or absorption of calories. The main treatment modalities for overweight and individuals with obesity remain dieting and physical exercise.

<span class="mw-page-title-main">Motilin</span>

Motilin is a 22-amino acid polypeptide hormone in the motilin family that, in humans, is encoded by the MLN gene.

<span class="mw-page-title-main">Growth hormone secretagogue receptor</span> Protein-coding gene in the species Homo sapiens

Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.

<span class="mw-page-title-main">GHRP-6</span> Chemical compound

Growth hormone-releasing peptide 6 (GHRP-6), also known as growth hormone-releasing hexapeptide, is one of several synthetic met-enkephalin analogues that include unnatural D-amino acids, were developed for their growth hormone-releasing activity and are called growth hormone secretagogues. They lack opioid activity but are potent stimulators of growth hormone (GH) release. These secretagogues are distinct from growth hormone releasing hormone (GHRH) in that they share no sequence relation and derive their function through activation of a completely different receptor. This receptor was originally called the growth hormone secretagogue receptor (GHSR), but due to subsequent discoveries, the hormone ghrelin is now considered the receptor's natural endogenous ligand, and it has been renamed as the ghrelin receptor. Therefore, these GHSR agonists act as synthetic ghrelin mimetics.

<span class="mw-page-title-main">Ibutamoren</span> Experimental drug

Ibutamoren (INN) is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin. It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.

<span class="mw-page-title-main">SM-130686</span> Chemical compound

SM-130686 is a small-molecule drug which acts as a potent, orally-active agonist of the ghrelin/growth hormone secretagogue receptor (GHSR) and growth hormone secretagogue, with around half the potency of the endogenous agonist ghrelin as a stimulator of growth hormone release. It produces dose-dependent increases in muscle mass and decrease in body fat, and is under investigation for the treatment of growth hormone deficiency and other medical conditions. Concerns about its potential use as a performance-enhancing drug for athletes have led to the development of urine tests for SM-130686 and other GHSR agonists, even though no drugs from this class have yet progressed to clinical use.

<span class="mw-page-title-main">Tabimorelin</span> Chemical compound

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.

An orexigenic, or appetite stimulant, is a drug, hormone, or compound that increases appetite and may induce hyperphagia. This can be a medication or a naturally occurring neuropeptide hormone, such as ghrelin, orexin or neuropeptide Y, which increases hunger and therefore enhances food consumption. Usually appetite enhancement is considered an undesirable side effect of certain drugs as it leads to unwanted weight gain, but sometimes it can be beneficial and a drug may be prescribed solely for this purpose, especially when the patient is suffering from severe appetite loss or muscle wasting due to cystic fibrosis, anorexia, old age, cancer or AIDS. There are several widely used drugs which can cause a boost in appetite, including tricyclic antidepressants (TCAs), tetracyclic antidepressants, natural or synthetic cannabinoids, first-generation antihistamines, most antipsychotics and many steroid hormones. In the United States, no hormone or drug has currently been approved by the FDA specifically as an orexigenic, with the exception of Dronabinol, which received approval for HIV/AIDS-induced anorexia only.

Cyril Y. Bowers, M.D., Emeritus Professor of Medicine at Tulane University School of Medicine, attended medical school at the University of Oregon and did an internship at the University of Washington. He then studied biochemistry at Cornell University and attended the Postgraduate School of Medicine at the University of Pennsylvania. From 1961-2004 he was the director of the Section of Endocrinology & Metabolism in the Department of Medicine at Tulane University School of Medicine. Dr. Bowers has served on the editorial board of several endocrine journals, was a member of the National Institute of Diabetes and Digestive and Kidney Diseases Study Section for eight years and has written over 400 articles in peer reviewed journals including chapters in books and over 200 abstracts.

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.

<span class="mw-page-title-main">Macimorelin</span> Chemical compound

Macimorelin (INN) – or Macrilen – is a drug that was developed by Æterna Zentaris for use in the diagnosis of adult growth hormone deficiency. Macimorelin acetate, the salt formulation, is a synthetic growth hormone secretagogue receptor agonist. It is a growth hormone secretagogue receptor agonist causing release of growth hormone from the pituitary gland. Macimorelin acetate is described chemically as D-Tryptophanamide, 2-methylalanyl-N-[(1R)-1-(formylamino)-2-(1H-indol-3-yl)ethyl]-acetate.

<span class="mw-page-title-main">Pralmorelin</span> Chemical compound

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).

<span class="mw-page-title-main">Anamorelin</span> Chemical compound

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.

<span class="mw-page-title-main">Relamorelin</span> Chemical compound

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.

<span class="mw-page-title-main">Ipamorelin</span> Peptide selective agonist of the ghrelin/growth hormone secretagogue receptor

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.

<span class="mw-page-title-main">Examorelin</span> Chemical compound

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.

<span class="mw-page-title-main">Ulimorelin</span> Chemical compound

Ulimorelin is a drug with a modified cyclic peptide structure which acts as a selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a).. Unlike many related drugs, ulimorelin has little or no effect on growth hormone (GH) release in rats. 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. It has been researched for enhancing gastrointestinal motility, especially in gastroparesis and in aiding recovery of bowel function following gastrointestinal surgery, where opioid analgesic drugs used for post-operative pain relief may worsen existing constipation. While ulimorelin has been shown to increase both upper and lower gastrointestinal motility in rats, and showed promising results initially in humans, it failed in pivotal clinical trials in post operative ileus.

<span class="mw-page-title-main">Semaglutide</span> Anti-diabetic medication of GLP-1 receptor agonist class

Semaglutide, sold under the brand names Ozempic, Wegovy and Rybelsus, is an antidiabetic medication used for the treatment of type 2 diabetes and an anti-obesity medication used for long-term weight management, developed by Novo Nordisk in 2012.

References

  1. 1 2 3 4 "FDA Approves Elura for Weight Loss in Cats with Chronic Kidney Disease". U.S. Food and Drug Administration. 19 October 2020. Retrieved 12 December 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  2. ↑ Khojasteh-Bakht SC, O'donnell JP, Fouda HG, Potchoiba MJ (January 2005). "Metabolism, pharmacokinetics, tissue distribution, and excretion of [14C]CP-424391 in rats". Drug Metabolism and Disposition. 33 (1): 190–9. doi:10.1124/dmd.104.001065. PMID   15486077. S2CID   20760627.
  3. ↑ "Entyce". U.S. Food and Drug Administration (FDA). Retrieved 12 December 2022.
  4. ↑ "Elura". U.S. Food and Drug Administration (FDA). Retrieved 12 December 2022.
  5. ↑ Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Murray MC, et al. (November 2002). "Discovery and biological characterization of capromorelin analogues with extended half-lives". Bioorganic & Medicinal Chemistry Letters. 12 (22): 3279–82. doi:10.1016/s0960-894x(02)00734-5. PMID   12392732.
  6. ↑ Carpino PA, Lefker BA, Toler SM, Pan LC, Hadcock JR, Cook ER, et al. (February 2003). "Pyrazolinone-piperidine dipeptide growth hormone secretagogues (GHSs). Discovery of capromorelin". Bioorganic & Medicinal Chemistry. 11 (4): 581–90. doi:10.1016/s0968-0896(02)00433-9. PMID   12538023.
  7. ↑ "Aratana Therapeutics Granted FDA Approval of Entyce (capromorelin oral solution)". Aratana Therapeutics. 17 May 2016. Retrieved 12 December 2022– via PR Newswire.
  8. ↑ Pan LC, Carpino PA, Lefker BA, Ragan JA, Toler SM, Pettersen JC, et al. (February 2001). "Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue". Endocrine. 14 (1): 121–32. doi:10.1385/ENDO:14:1:121. PMID   11322494. S2CID   46978604.
  9. ↑ White HK, Petrie CD, Landschulz W, MacLean D, Taylor A, Lyles K, et al. (April 2009). "Effects of an oral growth hormone secretagogue in older adults". The Journal of Clinical Endocrinology and Metabolism. 94 (4): 1198–206. doi: 10.1210/jc.2008-0632 . PMID   19174493.
  10. ↑ Rhodes L, Zollers B, Wofford JA, Heinen E (February 2018). "Capromorelin: a ghrelin receptor agonist and novel therapy for stimulation of appetite in dogs". Veterinary Medicine and Science. 4 (1): 3–16. doi:10.1002/vms3.83. PMC   5813110 . PMID   29468076.
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