GHRP-2 (Pralmorelin): A Synthetic Growth Hormone Secretagogue

Research summary. GHRP-2 (Growth Hormone-Releasing Peptide 2), also known by the development name pralmorelin, is a synthetic hexapeptide growth hormone secretagogue. It belongs to the pioneering class of GHRPs developed by Cyril Bowers and colleagues at Tulane University in the late 1970s and 1980s — work that ultimately led to the discovery of the endogenous ligand ghrelin and its receptor (GHS-R1a). GHRP-2 is one of the more potent members of the GHRP family at this receptor and remains a reference test peptide for evaluating the GH-IGF-1 axis in research contexts.

Molecular profile

• Sequence: D-Ala-D-2Nal-Ala-Trp-D-Phe-Lys-NH₂
• Molecular formula: C₄₅H₅₅N₉O₆
• Molecular weight: ~817.99 g/mol
• PubChem CID: 6918245
• CAS Number: 158861-67-7
• Synonyms: pralmorelin, KP-102, GPA-748, WAY-GPA-748

The peptide includes two D-amino-acid residues (D-Ala at position 1 and D-2-naphthylalanine at position 2) and an unnatural aromatic side chain that together confer enzymatic stability while preserving GHS-R1a engagement. The C-terminal amide is also important for activity.

Mechanism of action

GHRP-2 binds and activates the growth hormone secretagogue receptor type 1a (GHS-R1a), the same receptor engaged by the endogenous ligand ghrelin. Receptor activation produces:

• Stimulation of GH release from anterior pituitary somatotrophs through Gαq-mediated phospholipase C activation, IP3 generation, and calcium mobilisation.
• Synergy with GHRH. GHRP-2 acts at a different receptor than GHRH (which engages GHRHR), and the two pathways converge on GH release with greater than additive effects when administered in combination — the basis for the common GHRH+GHRP combination strategy in research.
• Modulation of appetite signalling. GHS-R1a activation in hypothalamic feeding circuits drives orexigenic (appetite-stimulating) effects, paralleling the role of endogenous ghrelin.
• Possible cardiac effects. GHS-R1a expression in cardiomyocytes has supported investigation of direct cardiac actions independent of GH release.

Preclinical and clinical research highlights

Diagnostic GH stimulation testing. GHRP-2 is approved in some jurisdictions (notably Japan, where it is marketed as KAATSU pralmorelin) as a diagnostic test agent for evaluation of growth hormone deficiency in adults and children. In this application, a single intravenous dose is followed by serial measurement of plasma GH to assess somatotroph reserve.

Pediatric short-stature investigation. Phase 2 clinical trials examined GHRP-2 as a potential alternative to recombinant human growth hormone for pediatric short stature. The molecule did not advance to broad regulatory approval in this indication.

Appetite stimulation research. GHRP-2's reliable orexigenic activity has supported its investigation in cachexia and appetite-loss research contexts in animal models.

Sleep architecture. Human studies have reported that GHRP-2 increases slow-wave sleep (stages 3 and 4) by approximately 50% and modestly increases REM sleep duration, consistent with the known role of GH-axis activity in sleep architecture regulation.

Cardiac protection. Studies of fetal cardiomyocyte preparations and adult cardiac tissue have reported that GHRP-2 and the related GHRP analogue hexarelin reduce apoptosis in ischaemia-reperfusion preparations, attributed to GHS-R1a-independent activity at distinct cardiac receptor sites.

Skeletal muscle. Studies in cachectic and stressed-animal models have reported preservation of lean mass with GHRP-2 administration, attributed to combined effects on GH-IGF-1 signalling and on protein-degradation pathways including atrogin-1 and MuRF1 expression.

Oral bioactivity. GHRP-2 retains activity by oral and sublingual routes (with reduced bioavailability relative to subcutaneous injection but functional GH-releasing activity), distinguishing it from many peptide hormones that require injection.

Position in the GHRP family

GHRP-2 sits alongside several related compounds in the GHRP family:

• GHRP-6: The original prototype of the class, with similar GH-releasing activity but more pronounced appetite stimulation
• Hexarelin: A close analogue with stronger reported cardiac effects
• Ipamorelin: A more selective GHS-R1a agonist with minimal cortisol or prolactin effects
• Ibutamoren / MK-677: A non-peptide small molecule with the same receptor target but oral bioavailability and an extended half-life

In research contexts, GHRP-2 is often combined with a GHRH analogue (such as CJC-1295 or sermorelin) to engage both branches of the GH-axis simultaneously.

Current research status

GHRP-2 is approved as a diagnostic agent in some jurisdictions but is not approved as a therapeutic for ongoing dosing in major regulatory markets. It is listed by the World Anti-Doping Agency as a prohibited substance under category S2 (peptide hormones, growth factors, related substances and mimetics). Active research applications include:

• GH-axis evaluation in clinical and translational research
• Cachexia and appetite-loss preclinical models
• Sleep architecture and GH-axis biology research
• Cardiac protection mechanistic studies

Key takeaways for researchers

• GHRP-2 is a synthetic hexapeptide GHS-R1a agonist with potent GH-releasing activity.
• It synergises with GHRH-class peptides through engagement of a distinct receptor.
• Reported applications include GH stimulation testing, appetite stimulation, sleep architecture studies, and cardiac protection research.
• It is on the WADA Prohibited List.
• It is approved in some jurisdictions as a diagnostic agent (notably in Japan as pralmorelin) but is not approved for therapeutic dosing.

References

1. Bowers CY. History to the discovery of ghrelin. Methods in Enzymology. 2012;514:3–32.

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This article is provided for educational and research purposes only. GHRP-2 is a research peptide. It is not approved as a therapeutic agent in major Western markets and is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease or condition outside of jurisdictions where it is legally licensed and supervised by qualified clinicians. GHRP-2 is listed by the World Anti-Doping Agency as a prohibited substance. All research work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.