![]() | |
Clinical data | |
---|---|
Other names | L-Histidyl-2-methyl-D-tryptophyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide |
Routes of administration | Intravenous, subcutaneous, intranasal, oral [1] |
ATC code |
|
Pharmacokinetic data | |
Elimination half-life | ~55 minutes [2] |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
IUPHAR/BPS | |
ChemSpider | |
UNII | |
ChEMBL | |
CompTox Dashboard (EPA) | |
Chemical and physical data | |
Formula | C47H58N12O6 |
Molar mass | 887.059 g·mol−1 |
3D model (JSmol) | |
| |
|
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]
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]