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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.
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.
There are conflicting reports on the ability of examorelin to
elevate insulin-like growth factor 1 (IGF-1) andinsulin-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. 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, 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. Pre-administration of GH blunts the
GH-releasing effect of examorelin, while, in contrast, fully
abolishing the effect of GHRH. Pre-treatment with IGF-1
also blunts the GH-elevating effect of examorelin.
Testosterone, testosterone enanthate, andethinylestradiol, though
not oxandrolone, have been found to significantly potentiate the
GH-releasing effects of examorelin in humans. 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.
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).
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.