GHRP-2 (pralmorelin)
pralmorelin, pralmorelin hydrochloride, KP-102, GPA-748, growth hormone-releasing peptide 2
GHRP-2, generically named pralmorelin, is a synthetic hexapeptide agonist at the ghrelin receptor and one of the most potent acute stimulators of growth hormone release known. It is the only compound in the GHRP family with any regulatory approval anywhere: Japan licensed it in 2004 as a single-dose intravenous diagnostic agent for growth hormone deficiency. That approval is for one injection to run a test, not for treatment, and the therapeutic evidence is thin.
Mechanism
GHRP-2 is an agonist at the growth hormone secretagogue receptor 1a, the ghrelin receptor. It acts at two levels simultaneously. At the pituitary somatotroph, GHS-R1a couples through Gq to phospholipase C, raising inositol trisphosphate and diacylglycerol, mobilising intracellular calcium and triggering growth hormone exocytosis. At the hypothalamic arcuate nucleus, agonism suppresses somatostatin tone and amplifies endogenous GHRH output, which is why GHRP-2's full effect depends on an intact hypothalamic GHRH supply, and why it acts synergistically with GHRH rather than merely additively. That synergy, demonstrated in humans since Bowers described it for this peptide family in 1990, is a genuine pharmacological phenomenon and underlies the combined GHRH-plus-GHRP stimulation tests used clinically.
Unlike ipamorelin, GHRP-2 is not selective for the somatotroph. Alongside growth hormone it raises ACTH, cortisol and prolactin, and it stimulates appetite. The appetite effect is not incidental. It is the direct consequence of GHS-R1a agonism in the arcuate nucleus, where activation of NPY/AgRP neurons drives food-seeking. GHRP-2 was in fact one of the compounds used to demonstrate that the ghrelin receptor is an orexigenic target in humans. Its potency as a growth hormone releaser is what made it useful diagnostically: in the validation study, healthy subjects reached peak growth hormone concentrations averaging 84.6 micrograms per litre, far higher than the insulin tolerance test produces, giving a wide separation from deficient patients.
What the research shows
The best-quality human evidence for GHRP-2 is diagnostic rather than therapeutic, and it is genuinely good. Chihara and colleagues studied 77 healthy subjects and 58 patients with growth hormone deficiency confirmed by an insulin tolerance test peak below 3 micrograms per litre, giving 100 micrograms of GHRP-2 intravenously and sampling growth hormone over two hours. Peak growth hormone occurred within 60 minutes in every subject and averaged 1.36 micrograms per litre in patients versus 84.6 in healthy subjects, and a cut-off of 15 micrograms per litre corresponded to the standard diagnostic threshold of 3 micrograms per litre on the insulin tolerance test. This is the basis of the Japanese approval, and it addresses a real clinical problem: the insulin tolerance test is contraindicated in many patients because of the risk of severe hypoglycaemia.
The therapeutic evidence is a different matter entirely. Mericq and colleagues gave six prepubertal children with growth hormone deficiency stepwise increasing subcutaneous doses of GHRP-2 (0.3, 1.0 and 3.0 micrograms per kilogram per day) over successive two-month periods across eight months. Growth velocity was higher during treatment than before or after, and no adverse effects were seen, but IGF-1 and IGFBP-3 did not increase, which is a significant disconnect, and six children in an uncontrolled dose-escalation design cannot establish efficacy; the authors themselves concluded that longer-acting formulations would be needed for therapeutic use. Laferrère and colleagues infused GHRP-2 into seven lean healthy men and found they ate 35.9 per cent more at a subsequent buffet meal, with every subject increasing intake, a clean demonstration of the orexigenic effect, in seven people.
So the honest position is this. GHRP-2 reliably and potently releases growth hormone in humans; that is well replicated and regulator-endorsed for diagnostic use. It reliably increases appetite. Beyond a single injection, almost nothing is established: no adequately powered trial has tested repeated GHRP-2 for growth, body composition, recovery, or any other therapeutic outcome, and the one small paediatric treatment study raised the awkward finding that growth hormone went up while IGF-1 did not.
Evidence assessment
Limited evidence
Well-replicated acute pharmacology and a Japanese regulatory approval for single-dose diagnostic use only; therapeutic evidence is confined to uncontrolled studies of six or seven participants (one of which found no rise in IGF-1) with no adequately powered controlled trial of repeated dosing for any outcome.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency Mixed evidence
Peak GH occurred within 60 minutes in all subjects and was 1.36 micrograms/L in patients versus 84.6 in healthy subjects; a cut-off of 15 micrograms/L corresponded to the 3 micrograms/L insulin tolerance test threshold.
Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children Limited evidence
Growth velocity was higher during GHRP-2 treatment than during pretreatment and post-treatment evaluations and no adverse effects were seen, but IGF-1 and IGFBP-3 did not change; the authors concluded longer-acting formulations would be needed for therapeutic application.
Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men Limited evidence
Participants ate 35.9 per cent more during GHRP-2 infusion than saline, with every subject increasing intake.
Pharmacokinetics and pharmacodynamics of growth hormone-releasing peptide-2: a phase I study in children Limited evidence
GHRP-2 produced a predictable and significant rise in plasma GH, peaking at 50.7 ng/mL at about 0.42 hours, with a terminal half-life of approximately 0.55 hours.
Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone Mixed evidence
Established that GHRP-family peptides release GH in humans and act synergistically with GHRH, producing a greater response than either agent alone.
Safety
The safety record covers single diagnostic doses, and within that narrow frame it is good. GHRP-2 has been given as a one-off intravenous injection to hundreds of adults and children in validation studies without significant adverse events, which is why Japanese regulators approved it as a test agent. Repeated dosing is a different question and largely unanswered. Two effects intrinsic to the compound matter for anyone considering ongoing use. GHRP-2 raises ACTH, cortisol and prolactin alongside growth hormone; the acute rises are modest, but the consequences of driving the hypothalamic-pituitary-adrenal axis daily for months have never been characterised. And it substantially increases appetite and food intake, by roughly a third in the one controlled feeding study, which is a therapeutic effect in cachexia and an unwanted one in most other contexts. The small paediatric study found no adverse effects over eight months but also found that IGF-1 and IGFBP-3 failed to rise, suggesting the growth hormone released may not translate into the expected downstream signalling. Class concerns (glucose intolerance, fluid retention, arthralgia, and neoplasia risk from sustained IGF-1 elevation) remain untested. Unregulated GHRP-2 has no verified identity, purity, sterility or endotoxin testing.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No UK marketing authorisation. Supply for human use is unlawful under the Human Medicines Regulations 2012. Available only as a laboratory research chemical, with the MHRA treating dosing or administration guidance as marketing an unlicensed medicine. |
| United States | Not approved by the FDA for any indication. It is not on Category 1 of the FDA's interim 503A bulk drug substances list and cannot lawfully be used in human compounding. Sold online under a 'for research use only' label, which carries no regulatory meaning regarding identity, purity or safety and serves mainly to permit the sale of an unapproved drug to consumers. |
| WADA (sport) | Prohibited at all times under section S2.2.4 of the WADA Prohibited List, which names GHRP-2 (pralmorelin) explicitly among prohibited GH-releasing peptides. Validated urine assays for pralmorelin and its metabolites have been published and are used in anti-doping testing. |
Questions
Yes, but only in Japan and only as a diagnostic agent. Japanese regulators approved pralmorelin in 2004 as a single-dose intravenous test for growth hormone deficiency. That is an approval for one injection to run a diagnostic test, not for repeated therapeutic use. It is not approved in the US, UK or EU for anything.
Both are ghrelin receptor agonists, but GHRP-2 is not selective: it raises ACTH, cortisol and prolactin, and stimulates appetite substantially, alongside growth hormone. Ipamorelin releases growth hormone without those additional hormone effects. GHRP-2 is the more potent growth hormone releaser and the only one with a regulatory approval; ipamorelin is the cleaner one pharmacologically.
Yes, markedly. In a controlled feeding study, seven lean healthy men ate 35.9 per cent more at a buffet meal during GHRP-2 infusion than during saline, and every participant increased intake. This is a direct consequence of ghrelin receptor activation in the hypothalamus, not a side effect that can be engineered away.
Not reliably. In the one study of prolonged administration (six children with growth hormone deficiency treated for eight months), growth velocity rose but IGF-1 and IGFBP-3 did not increase at all. That disconnect between growth hormone release and downstream IGF-1 signalling is an unresolved problem for the therapeutic case.