GHRP-6 5mg Peptide

GHRP-6 is a synthetic hexapeptide with the sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2. It was not isolated from any tissue. Frank Momany and Cyril Bowers designed it at Tulane University from conformational energy calculations on a series of small peptides that had grown out of structure-activity work on met-enkephalin analogues, and reported it in Endocrinology in 1984. The pentapeptide His-D-Trp-Ala-Trp-D-Phe-NH2 already released growth hormone from cultured pituitary cells at 1 to 10 ng/mL; adding a C-terminal lysine produced the hexapeptide that the field came to call GHRP-6.

The compound mattered for a reason that has almost nothing to do with growth hormone itself. GHRP-6 released GH through a pathway that GHRH antagonists did not block, which meant a second, uncharacterised receptor system existed in the pituitary and hypothalamus. In 1996 a Merck group led by Andrew Howard used the secretagogue class as the pharmacological handle to clone that receptor from swine and human pituitary libraries and named it the growth hormone secretagogue receptor, GHS-R. It was an orphan: a G protein coupled receptor with a synthetic agonist and no known hormone. Three years later Masayasu Kojima and Kenji Kangawa purified the missing ligand from rat stomach, found it carried an n-octanoyl group on serine 3, and named it ghrelin.

So the usual order was reversed. The drug came first, the receptor second, the hormone third. GHRP-6 is the tool compound that made a gut hormone findable, and that history is the most durable thing about it. Volta Peptides supplies GHRP-6 as a 10 mg lyophilised vial for laboratory research only. It is not a therapeutic product and is not intended for human or veterinary use.

GHRP-6 is an agonist at GHS-R1a, the ghrelin receptor, a Gq-coupled G protein coupled receptor expressed on anterior pituitary somatotrophs and on neurons of the hypothalamic arcuate nucleus. Receptor occupancy drives phospholipase C, inositol trisphosphate and a rise in intracellular calcium, and the somatotroph releases stored growth hormone. In primary rat pituitary cell culture GHRP-6 releases GH with an EC50 of 2.2 plus or minus 0.3 nmol/L, and that value is the reference point against which ipamorelin and the other secretagogues in this class were benchmarked.

The pituitary is only half of it. Sarah Dickson and Simon Luckman injected rats with 50 micrograms of GHRP-6 and mapped c-fos messenger RNA in the arcuate nucleus thirty minutes later. Treated animals showed 23 plus or minus 2 activated cells per section against 2 plus or minus 1 in vehicle controls, and when they matched the activated cells against neurochemical markers on consecutive sections, 51 plus or minus 4 percent expressed neuropeptide Y and 23 plus or minus 1 percent expressed GH-releasing factor. GHRP-6 is therefore recruiting the same NPY population that governs feeding drive at the same time as it recruits the GHRH neurons that amplify the GH pulse. The appetite signal and the GH signal share an anatomical origin.

Bowers showed the third piece in healthy men in 1990: submaximal GHRP-6 given together with GHRH produced GH release that was synergistic rather than additive. Two independent receptor systems converge on the same secretory cell, which is why GHRP and GHRH analogues are studied in combination in the literature and why neither one substitutes for the other.

GHRP-6 also binds a receptor that has nothing to do with growth hormone. Working with a radioactive photoactivatable hexarelin derivative on rat cardiac membranes, Bodart and colleagues purified an 84 kDa binding protein and sequenced its deglycosylated N-terminus as rat CD36, the class B scavenger receptor expressed on cardiomyocytes, microvascular endothelium and macrophages. Hearts from CD36-null mice and from spontaneously hypertensive rats that are genetically CD36 deficient did not show the coronary response. Most of the cytoprotective work on GHRP-6 runs through this second receptor rather than through GHS-R1a.

Most peptides in a research catalogue are copies of something the body already makes. GHRP-6 is the opposite case: it is a synthetic molecule that proved a natural hormone had to exist before anyone had seen it.

The logic ran through pharmacology rather than biochemistry. Bowers had a hexapeptide that released growth hormone and could show, through antagonist experiments and through the synergy with GHRH in men, that it was not acting at the GHRH receptor. Something else in the pituitary and hypothalamus was binding it. In August 1996 Howard and 27 co-authors at Merck Research Laboratories reported in Science that they had cloned that binding site from swine and human pituitary and hypothalamic tissue. Their closing sentence said the quiet part directly: the pharmacology of the cloned receptor supported the notion that the secretagogues mimic an undiscovered hormone.

That undiscovered hormone turned up in a stomach. Kojima, Hosoda, Date, Nakazato, Matsuo and Kangawa at the National Cardiovascular Center in Osaka screened tissue extracts against the cloned GHS-R and purified a 28 amino acid peptide from rat stomach whose serine 3 residue carried an n-octanoyl group. Remove the acyl group and the activity vanished. They published it in Nature in December 1999 and named it ghrelin, after the Proto-Indo-European root for grow. The finding rewrote the physiology of appetite, energy balance and gastric signalling, and it started with a hexapeptide designed in Louisiana fifteen years earlier.

Vendor pages almost universally mention that ghrelin was discovered in 1999 and almost universally omit the direction of causality. GHRP-6 did not come after ghrelin as a synthetic mimic. Ghrelin came after GHRP-6, found using an assay that GHRP-6 made possible.

The human dose-response for GHRP-6 was published in 1990 and remains the cleanest set of numbers on the compound. Bowers, Reynolds, Durham, Barrera, Pezzoli and Thorner gave 18 normal men intravenous bolus GHRP-6 at three levels. Mean peak serum GH rose from 1.2 micrograms per litre on placebo to 7.6, 16.5 and 68.7 micrograms per litre at 0.1, 0.3 and 1.0 micrograms per kilogram respectively. The curve is steep: a tenfold change in the amount infused moved peak GH roughly ninefold.

The same study measured what else moved. Serum prolactin and cortisol rose about twofold above baseline, and only at the highest level tested. Luteinising hormone and TSH did not change over the first hour. Facial flushing lasting one to three minutes occurred in 16 of the 18 men, and that was attributed to the GHRH-(1-44)-NH2 arm rather than to the hexapeptide. No adverse clinical effects or laboratory abnormalities were reported for GHRP-6 itself in that cohort.

Ghigo and colleagues in Turin then asked whether the oral route worked and whether it kept working. Seven healthy women aged 65 to 82 took 300 micrograms per kilogram by mouth. The GH peak was 10.7 micrograms per litre with an area under the curve of 353 micrograms per litre per hour, significantly higher than the response to a maximally effective intravenous GHRH stimulus in the same subjects. After four days of twice-daily oral administration the response was undiminished and if anything larger, at 16.8 micrograms per litre. IGF-1 did not rise significantly over that interval, which is what a four day study of a pulsatile stimulus would be expected to show.

Two things follow. Oral GHRP-6 is genuinely active, which is unusual for a peptide, but the effective oral amount in that study was roughly three hundred times the intravenous amount that produced a comparable pituitary response in Bowers' men. And short-term repeated administration did not blunt the pituitary response, which is a narrower finding than the claim of no tachyphylaxis that circulates online: four days of oral administration in seven elderly women is not a statement about months of continuous exposure.

Four secretagogues in this catalogue share a receptor and differ in ways that a single word like stronger cannot capture. The clearest head-to-head numbers come from Kirsten Raun's 1998 characterisation of ipamorelin at Novo Nordisk, which benchmarked every compound against GHRP-6 in the same assays.

In conscious swine, GHRP-2 was the most potent, with an ED50 of 0.6 nmol/kg against 3.9 plus or minus 1.4 nmol/kg for GHRP-6 and 2.3 plus or minus 0.03 nmol/kg for ipamorelin. Potency and efficacy went in opposite directions. Maximum GH response was 74 plus or minus 7 ng/mL for GHRP-6, 65 plus or minus 0.2 for ipamorelin and 56 plus or minus 6 for GHRP-2. GHRP-2 reaches its ceiling at a smaller amount; GHRP-6 has the higher ceiling. Anyone summarising this as GHRP-2 being stronger has collapsed two different measurements into one word.

Selectivity is where the family genuinely separates. In the same swine work, both GHRP-6 and GHRP-2 raised plasma ACTH and cortisol. Ipamorelin did not, at amounts more than 200-fold above its ED50 for GH release, and none of the compounds tested moved FSH, LH, prolactin or TSH in that species. Arvat and Ghigo's group in Turin measured the human side and found that the ACTH and cortisol response to GHRP-2 and hexarelin at 1 and 2 micrograms per kilogram intravenously was comparable in size to the response to human CRH itself, while their prolactin-releasing activity was lower than that of TRH. The corticotroph effect of the older GHRPs is not a rounding error, and it is the single reason ipamorelin was developed.

Hexarelin, His-D-2-methylTrp-Ala-Trp-D-Phe-Lys-NH2, is GHRP-6 with a methyl group added to the D-tryptophan at position 2. It carries the strongest cardiac literature of the group and shares the CD36 binding that GHRP-6 has. Ipamorelin, Aib-His-D-2-Nal-D-Phe-Lys-NH2, was found in a series that deliberately deleted the central Ala-Trp dipeptide, which is why its selectivity profile is different in kind rather than in degree.

GHRP-6 has a reputation for provoking hunger more forcefully than the rest of the class. The mechanism supporting that reputation is solid; the quantitative human comparison behind it does not exist.

What is established: GHS-R1a is the ghrelin receptor, ghrelin is the principal peripheral orexigenic signal, and GHRP-6 activates arcuate NPY neurons in rats, which is exactly where a feeding signal would be expected to enter. Okada and colleagues showed that intracerebroventricular picomole amounts of a GHRP increased food intake in free-feeding rats while systemic injection at the same amounts did not reproduce it, and that a GHRH antagonist blocked the GHRH-driven feeding response but left the GHRP-driven response intact. The feeding effect runs through the secretagogue receptor, not through the GHRH pathway.

What is not established: a controlled human food-intake comparison between GHRP-6 and GHRP-2. The published human ad libitum feeding study in this class used GHRP-2. Laferrère and Bowers infused seven lean healthy men with GHRP-2 at 1 microgram per kilogram per hour or saline for 270 minutes and then measured intake at a buffet meal. Every subject ate more on GHRP-2, by 35.9 plus or minus 10.9 percent overall. There is no matched trial putting GHRP-6 against GHRP-2 for food intake in people, so the ranking that appears on every comparison page is an inference from receptor pharmacology and anecdote, not a measured result.

The direction of the appetite research has also inverted since the 1990s. Search the literature for GHRP-6 today and most of the hits are studies of [D-Lys3]-GHRP-6, the receptor antagonist, used to block ghrelin signalling in models of alcoholic hepatic steatosis, hepatic fatty acid oxidation in growing pigs, memory consolidation in rat amygdala and dentate gyrus, and stress activation in the hypothalamus. The antagonist has become the more widely used research reagent of the two.

The cardiovascular and cytoprotective literature on GHRP-6 does not run through the pituitary. It runs through CD36, and the identification was done the hard way. Bodart's group at the Université de Montréal labelled rat cardiac membranes with a radioactive photoactivatable hexarelin derivative, purified the labelled species by lectin affinity chromatography and preparative gel electrophoresis, and sequenced the N-terminus of the deglycosylated 84 kDa product. It was rat CD36. Perfused hearts responded to hexarelin with a dose-dependent rise in coronary perfusion pressure; hearts from CD36-null mice and from spontaneously hypertensive rats carrying a natural CD36 deficiency did not.

The cleanest demonstration that this arm is separable from growth hormone came from EP 80317, a GHRP-derived CD36 ligand with no GH-releasing activity at all. Marleau and colleagues gave apolipoprotein E deficient mice on an atherogenic diet 300 micrograms per kilogram daily and found aortic lesion area reduced by up to 51 percent on en face analysis, with total plasma cholesterol down 30 percent after twelve weeks. At the macrophage level the compound reduced internalisation of oxidised LDL and upregulated PPAR gamma, LXR alpha, ABCA1 and ABCG1. In apoE/CD36 double-deficient mice none of it happened, and the transporter genes did not move. Whatever GHRP-6 does to a heart or a macrophage, it is not doing it by raising GH.

That distinction matters for how the cytoprotection findings should be read. The same receptor turns up in granulation tissue, which is why the Cuban wound-healing work treated CD36 as the target and used topical rather than systemic administration.

The only sustained clinical development programme for GHRP-6 has been run out of the Center for Genetic Engineering and Biotechnology in Havana, largely by Jorge Berlanga-Acosta and Diana García-del-Barco-Herrera, latterly in collaboration with the Shanghai Institute of Materia Medica. It is almost invisible in English-language product descriptions, and it is the only place where GHRP-6 has been given to patients under a protocol.

The clinical target is acute ischaemic stroke, and the intervention is a combination of recombinant epidermal growth factor with GHRP-6 rather than the hexapeptide alone. The Phase I/II trial, protocol IG/CIGB-845I/IC/1601, enrolled 36 patients within 12 hours of symptom onset between July 2017 and January 2018 and randomised them to 75 micrograms rEGF with either 3.5 mg or 5 mg GHRP-6 intravenously twice daily for seven days, or to standard care. Serious adverse events occurred in 9 of 16 control patients against 3 of 10 and 2 of 10 in the treated arms, and only two events in one patient were attributed to treatment. The primary endpoint was safety and it was met.

The Phase III follow-up, COURAGE-2, was published in the Journal of Clinical Neuroscience in 2026 and is the more instructive result because it is a negative one. It randomised 188 patients with baseline NIHSS scores of 5 to 20 to the combination or to standard care. In the intention-to-treat population there was no difference in modified Rankin Scale score, Barthel Index or survival. The trial missed its primary endpoint. In the prespecified severe-stroke subgroup, the 27 patients with NIHSS at or above 15, six-month mRS was 2.6 in the treated arm against 4.7 in controls, with a mortality hazard ratio of 0.18. Infarct volume reduction at 30 days favoured treatment in the middle cerebral artery territory.

A subgroup of 27 in a trial that failed overall is a hypothesis, not a result, and the authors described it that way. It is still more clinical evidence than most compounds in this category have, and it is worth knowing that the amounts used in those trials are two to three orders of magnitude above the micrograms per kilogram range that produces a maximal pituitary GH response, because in the stroke setting the GH axis is not the target.

The half-life figures attached to GHRP-6 in secondary sources range from about 15 minutes to about two and a half hours, and they disagree because no dedicated human pharmacokinetic study of GHRP-6 has been published. What exists is comparative rodent work. Johansen and colleagues at Novo Nordisk measured GHRP-6, GHRP-2 and three developmental secretagogues in male rats after intravenous bolus and found biexponential plasma decline for all of them, with the caveat printed in their own paper that sampling stopped at 40 minutes and does not exclude a longer terminal phase. Ipamorelin's systemic plasma clearance was five-fold lower than GHRP-6's. The elimination routes differ too: ipamorelin appeared mainly in urine, GHRP-6 predominantly in bile as intact peptide. After intranasal application, bioavailability was about 50 percent for GHRP-2 and lower for GHRP-6. Where a source states a precise GHRP-6 half-life without naming a species and a route, it is quoting the time to peak GH, which is a different quantity.

On identity, the widely reproduced figures are worth stating precisely because they are frequently mixed up. The average molecular weight of the free base is 873.0 g/mol; 872.44 is the monoisotopic mass, and the two are not interchangeable on a certificate of analysis. The molecular formula is C46H56N12O6. The PubChem record is CID 4345065. Two of the three catalogue entries that publish a CID for this compound point somewhere else.

The C-terminal primary amide and the D-configuration at positions 2 and 5 are structural, not decorative. The D residues resist aminopeptidase cleavage and hold the backbone in a conformation the GHS-R1a pocket accepts, which is why a one-letter representation written in uppercase, or a sequence quoted as the free acid without the terminal NH2, describes a different molecule from the one in the vial.

GHRP-6 is normally supplied as the acetate salt, and acetate carries mass. A vial's gross fill weight is not its net peptide content, and a certificate of analysis that reports RP-HPLC area purity without a net peptide content determination has answered only half the question. Purity figures quoted to three decimal places exceed what area-percent integration can resolve. Lyophilised material is stored at minus 20 degrees Celsius or colder, protected from light and moisture; peptide in aqueous solution is handled cold, aliquoted to avoid repeated freeze-thaw cycles, and treated as having a working life measured in weeks rather than months.