Hexarelin Acetate 5mg Peptide

Hexarelin, which carries the international nonproprietary name examorelin, is a synthetic hexapeptide growth hormone secretagogue with the sequence His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2. It is a single-residue redesign of GHRP-6: the D-tryptophan in position two carries a methyl group on the indole ring, and nothing else about the backbone changes. Deghenghi and colleagues introduced that substitution in 1994 specifically because 2-methyl-tryptophan is chemically more stable than tryptophan, and reported in Life Sciences that the resulting hexapeptide released growth hormone in conscious 10-day-old rats and in anaesthetised adult male rats, with peak plasma GH within 10 minutes of an intravenous dose.

The word acetate on a vial label names the counter-ion, not a second compound. Hexarelin has three basic sites that carry positive charge at neutral pH: the N-terminal amine, the histidine imidazole and the lysine side chain. After preparative HPLC the peptide is isolated as a salt, and acetate is the counter-ion paired with those charges. The free base is C47H58N12O6 at 887.0 g/mol; the monoacetate is C49H62N12O8 at 947.1 g/mol. Both are hexarelin. The acetate dissociates the instant the powder meets water.

Two things make hexarelin more than a stronger GHRP-6. The first is a second molecular target in the heart, CD36, which has nothing to do with growth hormone and which was identified by photoaffinity labelling of rat cardiac membranes. The second is a measured, reversible fall in the GH response across weeks of repeated exposure, quantified in a 16 week study in healthy elderly volunteers and rarely mentioned on pages selling the compound.

The growth hormone arm runs through GHS-R1a, the ghrelin receptor, expressed on pituitary somatotrophs and in the hypothalamus. In humans that arm is largely hypothalamus-dependent. Loche and colleagues gave 2 micrograms per kilogram of hexarelin intravenously to 15 children and 4 adults with growth hormone deficiency in 1995: patients with idiopathic deficiency responded much as 45 short normal control children did, while patients whose deficiency came from pituitary stalk interruption showed an absent or blunted response. A peptide acting only on the somatotroph would not care whether the stalk was intact.

Hexarelin and GHRH converge on the same cell through different receptors, which is why their effects add. Arvat and colleagues gave 2 micrograms per kilogram intravenously to 13 young and 16 elderly normal men in 1994. In the young group the GH area under the curve from 0 to 120 minutes was 4849 plus or minus 601 micrograms times minutes per litre for hexarelin, while an equal 2 microgram per kilogram dose of GHRH produced a significantly smaller response, reported as 1455 plus or minus 102 at P less than 0.02. Adding GHRH to hexarelin raised the young response to 7725 plus or minus 503 micrograms times minutes per litre. The response to hexarelin alone was less than half as large in the elderly group, 2112 plus or minus 683, and arginine restored it there while adding nothing in the young.

The cardiac arm does not use GHS-R1a at all. Bodart and colleagues labelled rat cardiac membranes with a radioactive photoactivatable hexarelin derivative in 2002, purified the labelled protein by lectin affinity chromatography and preparative gel electrophoresis, and sequenced the N-terminus of the deglycosylated product. It was rat CD36, an 84 kDa multifunctional glycoprotein expressed in cardiomyocytes and microvascular endothelial cells. Hexarelin raised coronary perfusion pressure dose-dependently in perfused hearts, and that response was absent in hearts from CD36-null mice and from spontaneously hypertensive rat strains genetically deficient in CD36.

Locatelli and colleagues had already shown in 1999 that the cardiac effect survives removal of the pituitary. Hypophysectomised rats given hexarelin at 80 micrograms per kilogram for 7 days were protected against the worsened ischemia-reperfusion damage that hypophysectomy causes, with lower left ventricular end diastolic pressure, less creatine kinase in the perfusate and better recovery of contractility. Growth hormone at 400 micrograms per kilogram produced similar results. EP 51389, another GH-releasing peptide that does not bind cardiac tissue, produced none.

There is a third category of binding site. Muccioli and colleagues showed in 2004 that hexarelin, like ghrelin and MK-0677, suppressed isoproterenol-stimulated glycerol release from rat epididymal adipocytes across 1 to 1000 nM, in cells that do not express GHS-R1a messenger RNA at all. Binding experiments on those membranes identified a shared high-affinity site distinct from the ghrelin receptor.

By 1994 GHRP-6, GHRP-1 and GHRP-2 had all been shown to release growth hormone in several mammalian species. Deghenghi and colleagues at the University of Milan asked a narrow chemistry question: what happens if the tryptophan at position two is replaced with 2-methyl-tryptophan, which is chemically more stable? The answer, published in Life Sciences, was hexarelin.

The comparison in that paper is more restrained than the marketing that followed it. In anaesthetised adult male rats, intravenous GHRP-6 and intravenous hexarelin produced prompt GH release with peak levels inside 10 minutes, and at every dose tested the two peptides had similar effectiveness. Given subcutaneously, hexarelin produced a longer-lasting release and was described as slightly more effective than GHRP-6. That is a real difference, and it is a difference in duration and route behaviour rather than a step change in receptor potency.

Human work followed quickly. Laron and colleagues tested intranasal hexarelin at 20 micrograms per kilogram against 1 microgram per kilogram intravenously in 10 children with familial short stature and 2 adults with growth hormone deficiency, finding mean GH responses of 72.2 and 79.6 milliunits per litre respectively, with the intravenous peak at 15 to 30 minutes and the intranasal peak between 30 and 60 minutes. Plasma TSH fell significantly during both tests while staying inside the normal range, an incidental finding that has almost never been followed up.

The cardiac literature is the reason hexarelin is still being published on thirty years after it was made, and it is the part of the compound that vendor pages most often reduce to a single line about being good for the heart. The mechanism is specific, and it is not the ghrelin receptor.

Bodart and colleagues went looking for the molecular target directly. They labelled rat cardiac membranes with a radioactive photoactivatable hexarelin derivative, purified the labelled species through lectin affinity chromatography and preparative gel electrophoresis, and sequenced the N-terminus of the deglycosylated product. It was rat CD36, an 84 kDa multifunctional glycoprotein expressed in cardiomyocytes and microvascular endothelial cells. Perfused hearts responded to hexarelin with a dose-dependent rise in coronary perfusion pressure. Hearts from CD36-null mice did not, and neither did hearts from spontaneously hypertensive rat strains that are genetically CD36-deficient. The vasoconstrictive response tracked CD36 expression measured by immunoblot.

Demers and colleagues then mapped where on CD36 the peptide sits. Covalent photolabelling followed by enzymatic and chemical degradation narrowed the binding site to an 8 kDa fragment corresponding to residues Asn132 to Glu177, with cyanogen bromide cleavage implicating Met169 as the contact point inside the pocket. That domain overlaps the oxidised LDL binding region of CD36, residues Gln155 to Lys183, which supplies a direct mechanistic link between the cardiac binding site and the anti-atherosclerotic result later reported in ApoE-null mice: hexarelin can compete with modified lipoprotein for the same receptor surface on macrophages.

Whether CD36 engagement is protective or hazardous depends on the model, and the honest reading of the literature is that both have been reported. The Bodart group closed their paper by suggesting CD36 may mediate the coronary vasospasm seen in hypercholesterolemia and atherosclerosis. The outcome studies, meanwhile, are consistently favourable: less ischemia-reperfusion damage in hypophysectomised rats, less interstitial collagen in spontaneously hypertensive rats, preserved ejection fraction with lower troponin-I, IL-1beta and TNF-alpha after coronary ligation in mice, smaller infrarenal aortic diameter and suppressed NLRP3 inflammasome activation in elastase-induced abdominal aortic aneurysm in mice at 200 micrograms per kilogram twice daily, and smaller plaques in ApoE-null mice.

There are two human cardiac datasets, both acute and both small. Bisi and colleagues studied 7 men with growth hormone deficiency and 9 controls by equilibrium radionuclide angiocardiography after intravenous hexarelin: ejection fraction rose about 7 percentage points in both groups, with no change in catecholamines, mean blood pressure or cardiac output, and with a negligible GH response in the deficient group.

The stronger design is Broglio and colleagues in 2002, because it carries its own controls for the growth hormone hypothesis. Twenty-four men with coronary artery disease undergoing bypass surgery, mean age 59.5 years and mean baseline ejection fraction 57.2 percent, received hexarelin at 2 micrograms per kilogram intravenously, GHRH at the same dose, recombinant human growth hormone at 10 micrograms per kilogram, or placebo, with cardiac performance measured by intraoperative transoesophageal echocardiography and arterial catheterisation. Growth hormone itself, GHRH and placebo produced no haemodynamic effect at all. Hexarelin raised ejection fraction, cardiac index and cardiac output within 10 minutes, held the change out to 90 minutes and lowered wedge pressure, with heart rate no different from placebo and systemic vascular resistance index unchanged. The arm that raised circulating growth hormone most, recombinant GH, did nothing to the heart.

This is the most under-reported fact about hexarelin, and it was measured carefully. Rahim, O'Neill and Shalet gave 12 healthy elderly volunteers twice-daily subcutaneous hexarelin at 1.5 micrograms per kilogram of body weight for 16 weeks and repeatedly re-tested the acute GH response to a single injection. The mean GH area under the curve was 19.1 plus or minus 2.4 micrograms per litre per hour at week 0, 13.1 at week 1, 12.3 at week 4 and 10.5 at week 16. The change across the study was significant at P = 0.0003, with the week 4 and week 16 falls significant against baseline.

The recovery arm is what makes the finding usable. Four weeks after the 16 week period ended, hexarelin was given again and the area under the curve rose to 19.4 plus or minus 3.7, significantly higher than week 16 and statistically indistinguishable from week 0. The attenuation is partial and it reverses.

Serum IGF-1 and IGFBP-3 did not change significantly across the whole 20 weeks, and neither did total body fat, lean body mass or bone mineral density at week 16. Of the bone turnover markers measured, only the C-terminal propeptide of type I collagen rose significantly. The GH pulses were real and they shrank, and on this schedule they never translated into a measurable downstream change in the GH-IGF-1 axis.

Schedule is the variable, not the compound. Ghigo and colleagues found the opposite pattern with intermittent exposure: an 8 day course of intranasal hexarelin at roughly 18 micrograms per kilogram three times daily in 7 elderly subjects, and a 15 day course of oral hexarelin at roughly 300 micrograms per kilogram three times daily in 7 elderly women, both left the acute GH response intact, with a trend upward rather than down, and modestly raised IGFBP-3. Neither prolactin nor cortisol shifted on those schedules.

All four are ghrelin receptor agonists and all four release growth hormone. The differences that matter are selectivity, duration and the presence or absence of a second target.

Against GHRP-6, hexarelin is the methylated derivative. Head-to-head in anaesthetised rats the two were similarly effective intravenously at every dose tested, with hexarelin producing a longer-lasting and slightly larger response by the subcutaneous route. Hexarelin also binds cardiac CD36, and a structurally related secretagogue that does not bind cardiac tissue, EP 51389, produced no cardioprotection in the hypophysectomised rat model where hexarelin did.

Against GHRP-2, hexarelin is close to indistinguishable on the endocrine axis. Arvat and colleagues gave 6 normal young adults 1 and 2 micrograms per kilogram of each intravenously and found similar GH responses that were both higher than GHRH, similar prolactin responses that were lower than TRH, and similar ACTH and cortisol responses that were comparable to human CRH. The widely repeated claim that hexarelin is uniquely bad for cortisol among the GHRPs is not what that comparison found. Both peptides move ACTH and cortisol, by about the same amount.

Against ipamorelin the contrast is genuine and runs the other way. Raun and colleagues characterised ipamorelin, a pentapeptide with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2, as the first selective GHS-R agonist. In conscious swine, GHRP-6 and GHRP-2 both raised plasma ACTH and cortisol, while ipamorelin did not do so beyond what GHRH produced, and that selectivity held at doses more than 200-fold above its ED50 for GH release. Ipamorelin's GH potency in anaesthetised rats was comparable to GHRP-6 rather than superior, with an ED50 of 80 plus or minus 42 nmol per kilogram against 115 plus or minus 36 for GHRP-6. Choosing between them is a question of how much off-target pituitary signalling an experiment tolerates, not of which releases more growth hormone.

None of the other three has an equivalent body of cardiac work. That is the axis on which hexarelin is genuinely different.

Hexarelin acetate and hexarelin are the same peptide in different salt forms. Acetate is the counter-ion left paired with the peptide's basic groups after purification, and it is not covalently attached to anything.

The molecule carries three sites that can hold a positive charge near neutral pH: the free N-terminal amine, the imidazole ring of histidine and the epsilon-amine of lysine. Reversed-phase HPLC purification is normally run with an acidic modifier, so the isolated product comes off as a salt. Acetate is the preferred counter-ion for a research peptide because the common alternative, trifluoroacetate, is itself biologically active at concentrations that can confound a cell assay, and because acetate can be exchanged out by lyophilisation from dilute acetic acid.

The practical consequence is mass balance. The free base is 887.0 g/mol and the monoacetate is 947.1 g/mol, so a monoacetate is about 93.7 percent peptide by mass. Because there are three basic sites, the number of acetate equivalents actually present varies between lots, which is exactly why a certificate of analysis reports net peptide content separately from gross mass. A vial labelled by gross weight and a vial labelled by net peptide content do not hold the same number of moles.

The counter-ion does not appear in a mass spectrum of the peptide. Electrospray analysis of hexarelin acetate reports the free base mass, so a certificate showing an average mass near 887 for the neutral species, or a singly protonated ion near 888, is the correct result for an acetate salt rather than evidence that the material is unsalted.

The most complete disposition study is Roumi and colleagues in Drug Metabolism and Disposition. Male Sprague-Dawley rats received either a 5 microgram per kilogram intravenous bolus or single subcutaneous doses of 5, 10 and 50 micrograms per kilogram, with a tritium-labelled tracer arm at 1 microgram per kilogram to follow tissue distribution and excretion.

After intravenous administration the half-life was 75.9 plus or minus 9.3 minutes, systemic clearance 7.6 plus or minus 0.7 millilitres per minute per kilogram and the steady-state volume of distribution 744 plus or minus 81 millilitres per kilogram. Subcutaneous bioavailability was 64 percent. Clearance and volume of distribution corrected for bioavailability were dose-independent across the range tested, and areas under the curve rising in proportion to dose confirmed no accumulation. Kinetics appeared first order up to 50 micrograms per kilogram.

The elimination route is the surprising part. Radioactivity concentrated in kidney, liver and duodenum, and biliary excretion was the primary route: 60 percent of the dose appeared in bile, 22 percent in urine and 10 percent in faeces. Of the radioactivity recovered in bile, 90 percent was unchanged hexarelin, and 71 percent of urinary radioactivity was unchanged as well. A hexapeptide surviving hepatic transit and biliary excretion essentially intact is direct evidence that the 2-methyl-tryptophan substitution did what it was designed to do.

The half-life figures circulating on the open web are not measured human values. The rat number above is the one with a published methods section behind it, and the human evidence constrains the hormone response rather than the plasma concentration: peak GH within 15 to 30 minutes of an intravenous dose, falling back over the following few hours.

Renal ischemia-reperfusion. Guan and colleagues pretreated rats at 100 micrograms per kilogram daily for 7 days before inducing ischemic acute kidney injury, then assessed at 24 hours. Pretreated animals showed less tubular necrosis and dilatation, better serum creatinine and less apoptosis, with lower caspase-3, Bax and Bad and higher Bcl-2. Molecular docking pointed at MDM2, and both MDM2 and p53 expression were suppressed in vivo and in hypoxia-reoxygenated HK-2 cells.

Motor neuron disease models. Meanti and colleagues exposed SH-SY5Y human neuroblastoma cells expressing the SOD1-G93A mutant protein to 150 micromolar hydrogen peroxide for 24 hours. One micromolar hexarelin, and the related secretagogue JMV2894, protected against cytotoxicity by shifting apoptotic and survival signalling. This is cell culture work and should be read as such.

Chemotherapy-associated muscle wasting. Sirago and colleagues characterised mitochondrial homeostasis in the tibialis anterior of cisplatin-treated rats and found reduced biogenesis markers, reduced mitochondrial mass, altered fusion and fission indices, changed autophagy signalling and higher reactive oxygen species. Hexarelin antagonised that pattern, placing the mechanism at the mitochondrion rather than at the myofibril.

Adipose tissue. Muccioli and colleagues found that hexarelin reduced isoproterenol-stimulated glycerol release from rat epididymal adipocytes across a 1 to 1000 nM range, in a tissue that does not transcribe GHS-R1a. The binding site responsible is shared with acylated and des-acyl ghrelin and is distinct from the ghrelin receptor, so the compound has at least three pharmacologically separable targets across the body.

The structure says what to protect. Hexarelin contains two indole side chains, the 2-methyl-D-tryptophan at position two and the L-tryptophan at position four. Indoles are the residues most prone to photo-oxidation in a peptide, so amber vials and dark storage are not a formality for this compound in particular. The C-terminal primary amide removes the free carboxylate that would otherwise be a degradation site, and the two D-amino acids resist exopeptidase attack.

Lyophilised hexarelin acetate is a white to off-white powder. Colour in the cake, or a solution that is not clear and colourless once dissolved, is the first indication that something has gone wrong. Lyophilised material is normally held frozen for long-term storage and aqueous solutions cold and short-term, since a peptide in water is always less stable than a peptide in a dry cake regardless of sequence.

For identity, the two orthogonal measurements are reversed-phase HPLC for purity and mass spectrometry for identity. The mass to look for is the free base, near 887 for the neutral molecule, because the acetate counter-ion dissociates and is not observed. A certificate quoting 947 as a measured mass is reporting the salt formula rather than an observed ion. Amino acid analysis, or net peptide content by nitrogen determination, is what separates gross vial weight from actual peptide mass, and for a compound supplied as an acetate salt that gap is real.

Hexarelin has no registered interventional trials. A query of the ClinicalTrials.gov registry in August 2026 returns zero studies for the term under any of its names. That result needs one caveat: the registry only began accepting records in 2000, and the entire human hexarelin literature predates it, so the zero means no modern programme rather than proof that no sponsored study ever ran. The published human work is investigator-initiated pharmacology carried out largely between 1994 and 2002 at Turin, Manchester, Milan, Cagliari and Petah Tikva, with sample sizes in the single digits to low twenties.

That history explains a gap worth holding onto. There is a well-characterised acute endocrine response in humans, a well-characterised 16 week desensitisation curve in 12 elderly volunteers, and two small acute cardiac studies, one of them placebo and active-comparator controlled. There is no controlled human outcome data of any kind and no study longer than 20 weeks. The rest of the cardiac case rests on rodent models. PubMed indexes around 290 records naming hexarelin in the title or abstract, and the work published since the human studies stopped is overwhelmingly preclinical: rodent cardiac, renal, vascular and muscle models, plus cell culture.