Examorelin
Chemical compound
From Wikipedia, the free encyclopedia
Examorelin (INN; also known as hexarelin; developmental codes EP-23905 and MF-6003) 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.[3][4][5][6][7] 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.[5][6]
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| Other names | L-Histidyl-2-methyl-D-tryptophyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide |
| Routes of administration | Intravenous, subcutaneous, intranasal, oral[1] |
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| Elimination half-life | ~55 minutes[2] |
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| Formula | C47H58N12O6 |
| Molar mass | 887.059 g·mol−1 |
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Examorelin substantially and dose-dependently increases plasma levels of growth hormone (GH) in animals and humans.[2] 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.[2][8] 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.[2][9][10][11] Examorelin does not affect plasma levels of glucose, luteinizing hormone (LH), follicle-stimulating hormone (FSH), or thyroid-stimulating hormone (TSH) in humans.[2]
Examorelin releases more GH than does growth hormone-releasing hormone (GHRH) in humans,[8][12] 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.[13][14][15] Pre-administration of GH blunts the GH-releasing effect of examorelin, while, in contrast, fully abolishing the effect of GHRH.[14][16] Pre-treatment with IGF-1 also blunts the GH-elevating effect of examorelin.[17] Testosterone, testosterone enanthate, and ethinylestradiol, though not oxandrolone, have been found to significantly potentiate the GH-releasing effects of examorelin in humans.[18][19] 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.[20]
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).[21][22]
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.[6][23]