Growth hormone secretagogue

Hexarelin

ExamorelinEP-23905MF-6003Examorelina

Hexarelin (examorelin) is a synthetic hexapeptide growth hormone secretagogue and ghrelin-receptor (GHSR) agonist that reached Phase II trials but was never approved as a medicine.

Overview

Hexarelin, also known as examorelin (developmental codes EP-23905 and MF-6003), is a synthetic hexapeptide growth hormone-releasing peptide (GHRP) developed in the 1990s and derived structurally from GHRP-6. It is a potent and selective agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a), the same receptor targeted by the endogenous hormone ghrelin, even though GHRPs share no amino-acid sequence similarity with ghrelin or with growth hormone-releasing hormone (GHRH).

Receptor activation at the pituitary and hypothalamus stimulates the pulsatile release of growth hormone and, secondarily, IGF-1. In human research it also slightly and dose-dependently raises prolactin, ACTH, and cortisol. With long-term administration a partial and reversible tolerance to its GH-releasing effect develops, reported as roughly a 50-75% decrease in efficacy over the course of weeks to months. Its plasma half-life is short, on the order of about 55 minutes.

The compound (amino acid sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2) reached Phase II clinical trials for growth hormone deficiency and congestive heart failure but did not complete development and was never marketed. Beyond GH secretion, it has been studied preclinically for cardiotropic and cardioprotective ("cytoprotective") effects, including actions described as partly independent of growth hormone. It has never been approved by the FDA, EMA, MHRA, or any other regulator, is sold only as a research chemical, and is prohibited at all times in sport by WADA as a growth hormone secretagogue.

Mechanism, evidence & status

Hexarelin is a synthetic hexapeptide growth hormone-releasing peptide (GHRP) that acts as a potent agonist of the ghrelin/growth hormone secretagogue receptor (GHSR-1a) at the pituitary and hypothalamic level. Receptor activation stimulates pulsatile release of growth hormone (and secondarily IGF-1), and it shares no sequence homology with growth hormone-releasing hormone (GHRH) or with ghrelin. It also modestly raises prolactin, ACTH, and cortisol in research settings.

Human evidence: Preclinical and early-phase (Phase II) clinical studies; never approved
Regulatory status: Not approved by the FDA, EMA, MHRA, or any regulator for any indication. Reached Phase II clinical trials (growth hormone deficiency, congestive heart failure) but was never marketed. Prohibited at all times in sport by WADA as a growth hormone secretagogue (Prohibited List section S2). Sold only as a research chemical; not a licensed medicine.

Research applications

Investigated in research as a tool to study GHSR-1a signaling and stimulated growth hormone / IGF-1 secretion.
Studied preclinically for cardiotropic and cardioprotective effects, including in isolated and denervated heart models.
Examined in early clinical research for growth hormone deficiency and congestive heart failure (Phase II, never approved).

Safety considerations

Not an approved drug anywhere; human safety has not been established by any regulator and the quality of research-chemical material is unverified.
Repeated administration produces partial, reversible tolerance, with reported efficacy reductions of roughly 50-75% over weeks to months in human studies (Wikipedia/clinical literature).
As a GHSR agonist it can transiently raise prolactin, ACTH, and cortisol; effects on cardiac function have been described in preclinical models.
Banned by WADA at all times in and out of competition.

References