Examorelin (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

; also known as hexarelin; developmental codes EP-23905 and MF-6003) is a potent,

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

, peptidic, orally-active, centrally-penetrant, and highly selective

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the ghrelin/growth hormone secretagogue receptor (GHSR) and a

growth hormone secretagogue Growth hormone secretagogues or GH secretagogues (GHSs) are a class of drugs which act as secretagogues (i.e., induce the secretion) of growth hormone (GH). They include agonists of the growth hormone secretagogue receptor, ghrelin/growth hormone s ...

which was developed by

Mediolanum Farmaceutici Mediolanum, the ancient city where Milan now stands, was originally an Insubrian city, but afterwards became an important Roman city in Northern Italy. The city was settled by a Celtic tribe belonging to the Insubres group and belonging to t ...

. It is a

hexapeptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ami ...

with the

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂ which was derived from

GHRP-6 Growth hormone-releasing peptide 6 (GHRP-6) (developmental code name SKF-110679), also known as growth hormone-releasing hexapeptide, is one of several synthetic met-enkephalin analogues that include unnatural D-amino acids, were developed for ...

. These GH-releasing peptides have no sequence similarity to ghrelin, but mimic ghrelin by acting as agonists at the

ghrelin Ghrelin (; or lenomorelin, INN) is a hormone primarily 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 ghrel ...

receptor. Examorelin substantially and dose-dependently increases plasma levels of

growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) 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 ...

(GH) in animals and humans. In addition, similarly to

pralmorelin Pralmorelin (INN) (brand name GHRP Kaken 100; former developmental code names KP-102, GPA-748, WAY-GPA-748), also known as pralmorelin hydrochloride ( JAN) and pralmorelin dihydrochloride (USAN), as well as, notably, growth hormone-releasing pept ...

(GHRP-2) and GHRP-6, it slightly and dose-dependently stimulates the release of

prolactin Prolactin (PRL), also known as lactotropin and mammotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secr ...

adrenocorticotropic hormone Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...

(ACTH), and

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

in humans. There are conflicting reports on the ability of examorelin to elevate

insulin-like growth factor 1 Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in tertiary structure, molecular structure to insulin which plays an important role in childhood growth, and has Anabolism, anabolic effects in adults. In the ...

(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. Examorelin does not affect plasma levels of

glucose Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...

(LH),

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH), or thyroid-stimulating hormone (TSH) in humans. Examorelin releases more GH than does

growth hormone-releasing hormone Growth may refer to: Biology * Auxology, the study of all aspects of human physical growth * Bacterial growth *Cell growth *Growth hormone, a peptide hormone that stimulates growth *Human development (biology) *Plant growth *Secondary growth, gro ...

(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 is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

testosterone enanthate Testosterone enanthate is used in the treatment of low testosterone levels in men. It is also used in hormone therapy for women and transgender men. It is given by injection into muscle or subcutaneously usually once every one to four weeks. ...

, and

ethinylestradiol Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. Ethinylestradiol was widely used for various indications such as the treatment of menopausal symptoms, gynecological ...

, though not

oxandrolone Oxandrolone is an androgen and synthetic anabolic steroid (AAS) medication to help promote weight gain in various situations, to help offset protein catabolism caused by long-term corticosteroid therapy, to support recovery from severe burns, t ...

, have been found to significantly potentiate the GH-releasing effects of examorelin in humans. In accordance, likely due to increases in

sex steroid Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects a ...

levels,

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a female, the testicles i ...

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 trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s for the treatment of

growth hormone deficiency Growth hormone deficiency (GHD), or hyposomatotropism, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height. Newborns may also present low blood ...

and

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF typically pr ...

but did not complete development and was never marketed.

References

{{GH/IGF-1 axis signaling modulators Experimental drugs Ghrelin receptor agonists Growth hormone secretagogues Hexapeptides World Anti-Doping Agency prohibited substances Experimental cardiovascular drugs

See also

References