Examorelin Explained

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.[1] [2] [3] [4] [5] 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.

Examorelin substantially and dose-dependently increases plasma levels of growth hormone (GH) in animals and humans. In addition, similarly to pralmorelin (GHRP-2) and GHRP-6, it slightly and dose-dependently stimulates the release of prolactin, adrenocorticotropic hormone (ACTH), and cortisol in humans.[6] There are conflicting reports on the ability of examorelin to elevate insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 1 (IGFBP-1) levels in humans, with some studies finding no increase and others finding a slight yet statistically significant increase.[7] [8] [9] Examorelin does not affect plasma levels of glucose, luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH) in humans.

Examorelin releases more GH than does growth hormone-releasing hormone (GHRH) in humans,[10] and produces synergistic effects on GH release in combination with GHRH, resulting in "massive" increases in plasma GH levels even with only low doses of examorelin.[11] [12] [13] Pre-administration of GH blunts the GH-releasing effect of examorelin, while, in contrast, fully abolishing the effect of GHRH.[14] Pre-treatment with IGF-1 also blunts the GH-elevating effect of examorelin.[15] Testosterone, testosterone enanthate, and ethinylestradiol, though not oxandrolone, have been found to significantly potentiate the GH-releasing effects of examorelin in humans.[16] [17] In accordance, likely due to increases in sex steroid levels, puberty has also been found to significantly augment the GH-elevating actions of examorelin in humans.[18]

A partial and reversible tolerance to the GH-releasing effects of examorelin occurs in humans with long-term administration (50–75% decrease in efficacy over the course of weeks to months).[19] [20]

Examorelin reached phase II clinical trials for the treatment of growth hormone deficiency and congestive heart failure but did not complete development and was never marketed.[21]

See also

Notes and References

  1. Book: Ganellin CR, Triggle DJ . Dictionary of Pharmacological Agents. 21 November 1996. CRC Press. 978-0-412-46630-4. 617–.
  2. Book: Morton IK, Hall JM . Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 6 December 2012. Springer Science & Business Media. 978-94-011-4439-1. 117–.
  3. Moulin A, Ryan J, Martinez J, Fehrentz JA . Recent developments in ghrelin receptor ligands . ChemMedChem . 2 . 9 . 1242–1259 . September 2007 . 17520591 . 10.1002/cmdc.200700015 . 24945528 .
  4. Wang Y, Tomlinson B . Tesamorelin, a human growth hormone releasing factor analogue . Expert Opinion on Investigational Drugs . 18 . 3 . 303–310 . March 2009 . 19243281 . 10.1517/13543780802707658 . 71177320 .
  5. Carpino PA . Recent developments in ghrelin receptor (GHS-R1a) agonists and antagonists. Expert Opinion on Therapeutic Patents. 12 . 11 . 2002 . 1599–1618 . 10.1517/13543776.12.11.1599 . 83645573 .
  6. Arvat E, di Vito L, Maccagno B, Broglio F, Boghen MF, Deghenghi R, Camanni F, Ghigo E . 6 . Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH . Peptides . 18 . 6 . 885–891 . 1997 . 9285939 . 10.1016/s0196-9781(97)00016-8 . 25480336 .
  7. Ghigo E, Arvat E, Gianotti L, Grottoli S, Rizzi G, Ceda GP, Boghen MF, Deghenghi R, Camanni F . 6 . Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging . European Journal of Endocrinology . 135 . 4 . 407–412 . October 1996 . 8921821 . 10.1530/eje.0.1350407 .
  8. Laron Z, Frenkel J, Deghenghi R, Anin S, Klinger B, Silbergeld A . Intranasal administration of the GHRP hexarelin accelerates growth in short children . Clinical Endocrinology . 43 . 5 . 631–635 . November 1995 . 8548949 . 10.1111/j.1365-2265.1995.tb02929.x . 30980163 .
  9. Frenkel J, Silbergeld A, Deghenghi R, Laron Z . Short term effect of intranasal administration of hexarelin--a synthetic growth hormone-releasing peptide. Preliminary communication . Journal of Pediatric Endocrinology & Metabolism . 8 . 1 . 43–45 . 1995 . 7584696 . 10.1515/jpem.1995.8.1.43 . 6791525 .
  10. Maccario M, Arvat E, Procopio M, Gianotti L, Grottoli S, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F, Ghigo E . 6 . Metabolic modulation of the growth hormone-releasing activity of hexarelin in man . Metabolism . 44 . 1 . 134–138 . January 1995 . 7854159 . 10.1016/0026-0495(95)90300-3 .
  11. Massoud AF, Hindmarsh PC, Brook CG . Hexarelin-induced growth hormone, cortisol, and prolactin release: a dose-response study . The Journal of Clinical Endocrinology and Metabolism . 81 . 12 . 4338–4341 . December 1996 . 8954038 . 10.1210/jcem.81.12.8954038 . free .
  12. Arvat E, Di Vito L, Gianotti L, Ramunni J, Boghen MF, Deghenghi R, Camanni F, Ghigo E . 6 . Mechanisms underlying the negative growth hormone (GH) autofeedback on the GH-releasing effect of hexarelin in man . Metabolism . 46 . 1 . 83–88 . January 1997 . 9005975 . 10.1016/s0026-0495(97)90173-6 .
  13. Arvat E, Gianotti L, Di Vito L, Imbimbo BP, Lenaerts V, Deghenghi R, Camanni F, Ghigo E . 6 . Modulation of growth hormone-releasing activity of hexarelin in man . Neuroendocrinology . 61 . 1 . 51–56 . January 1995 . 7731498 . 10.1159/000126827 .
  14. Massoud AF, Hindmarsh PC, Brook CG . Hexarelin induced growth hormone release is influenced by exogenous growth hormone . Clinical Endocrinology . 43 . 5 . 617–621 . November 1995 . 8548947 . 10.1111/j.1365-2265.1995.tb02927.x . 31571160 .
  15. Book: Owusu-Apenten R . Anabolic Dysfunction . Bioactive Peptides: Applications for Improving Nutrition and Health. https://books.google.com/books?id=JJ_MBQAAQBAJ&pg=PA292. 23 June 2010. CRC Press. 978-1-4398-1363-8. 292–.
  16. Loche S, Colao A, Cappa M, Bellone J, Aimaretti G, Farello G, Faedda A, Lombardi G, Deghenghi R, Ghigo E . 6 . The growth hormone response to hexarelin in children: reproducibility and effect of sex steroids . The Journal of Clinical Endocrinology and Metabolism . 82 . 3 . 861–864 . March 1997 . 9062497 . 10.1210/jcem.82.3.3795 . free .
  17. Loche S, Cambiaso P, Carta D, Setzu S, Imbimbo BP, Borrelli P, Pintor C, Cappa M . 6 . The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects . The Journal of Clinical Endocrinology and Metabolism . 80 . 2 . 674–678 . February 1995 . 7852535 . 10.1210/jcem.80.2.7852535 .
  18. Bellone J, Aimaretti G, Bartolotta E, Benso L, Imbimbo BP, Lenhaerts V, Deghenghi R, Camanni F, Ghigo E . 6 . Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, before and during puberty . The Journal of Clinical Endocrinology and Metabolism . 80 . 4 . 1090–1094 . April 1995 . 7714074 . 10.1210/jcem.80.4.7714074 .
  19. Rahim A, O'Neill PA, Shalet SM . Growth hormone status during long-term hexarelin therapy . The Journal of Clinical Endocrinology and Metabolism . 83 . 5 . 1644–1649 . May 1998 . 9589671 . 10.1210/jcem.83.5.4812 . free .
  20. Book: Ghigo E . Growth Hormone Secretagogues: Basic Findings and Clinical Implications. 1999. Elsevier. 978-0-444-82933-7. 178–.
  21. Suckling K . Discontinued drugs in 2005: cardiovascular drugs . Expert Opinion on Investigational Drugs . 15 . 11 . 1299–1308 . November 2006 . 17040192 . 10.1517/13543784.15.11.1299 . 21632578 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Examorelin".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.