GHRP-2

Growth Hormone Releasing Peptide-2 (GHRP-2), also known as KP-102 or Pralmorelin, is a synthetic hexapeptide developed as a second-generation growth hormone secretagogue. It acts as a potent agonist of the ghrelin receptor (GHS-R1a) and is recognized as one of the most potent stimulators of growth hormone release among the GHRP family, exceeding both GHRP-6 and GHRP-1 in GH-releasing efficacy. Structurally, GHRP-2 differs from GHRP-6 by the substitution of D-2-naphthylalanine (D-2-Nal) for D-tryptophan at the second position. This modification enhances binding affinity for GHS-R1a and produces a stronger and more sustained GH response. Importantly, GHRP-2 retains significant appetite-stimulating activity but to a lesser degree than GHRP-6, placing it pharmacologically between the highly orexigenic GHRP-6 and the appetite-neutral Ipamorelin. GHRP-2 has advanced further in clinical development than most GH secretagogues. In Japan, it received regulatory approval as Pralmorelin (marketed as GHRP Kaken 100) for the diagnostic assessment of growth hormone secretory capacity, validating its clinical utility and safety profile in human subjects. This approval has generated a substantial body of clinical pharmacology data that informs ongoing research applications.

GHRP-2 exerts its effects through receptor-mediated pathways that parallel but exceed those of GHRP-6: **High-Affinity GHS-R1a Agonism**: GHRP-2 binds to the growth hormone secretagogue receptor 1a with higher affinity than GHRP-6, owing to the D-2-Nal substitution that optimizes hydrophobic interactions within the receptor binding pocket. This produces more robust activation of phospholipase C, intracellular calcium release, and subsequent GH exocytosis from pituitary somatotrophs. **Hypothalamic GHRH Potentiation**: Like GHRP-6, GHRP-2 acts at the hypothalamic level to stimulate endogenous GHRH release and attenuate somatostatin tone. This central action amplifies the pituitary GH response and contributes to the synergistic interaction observed when GHRP-2 is co-administered with exogenous GHRH analogs. **Modulated Orexigenic Signaling**: GHRP-2 activates hypothalamic feeding circuits through GHS-R1a, but the appetite-stimulating effect is attenuated compared to GHRP-6. This partial modulation is attributed to differences in receptor activation kinetics and downstream signaling cascade engagement in NPY/AgRP neurons. **Cortisol and Prolactin Effects**: GHRP-2 produces dose-dependent increases in ACTH, cortisol, and prolactin, though the magnitude is somewhat less than GHRP-6 at equipotent GH-releasing doses. These effects reflect non-selective pituitary stimulation and are most pronounced at higher doses. **GH-Independent Cytoprotective Activity**: Emerging research suggests GHRP-2, like GHRP-6, may exert cytoprotective effects on cardiac and hepatic tissue through mechanisms independent of GH release, potentially involving CD36 and other non-GHS-R1a receptors.

GHRP-2 has been studied in clinical and preclinical contexts across multiple decades: **Comparative GH Release Potency**: Head-to-head studies have established GHRP-2 as the most potent GH secretagogue in the GHRP family. Research by Bowers and colleagues demonstrated that GHRP-2 elicits GH peaks approximately 20-30% higher than equimolar doses of GHRP-6, with a more sustained elevation profile. When combined with GHRH, the synergistic GH output exceeds either stimulus alone by 3-5 fold. **Diagnostic Application**: The approval of GHRP-2 (Pralmorelin) in Japan for GH provocative testing generated substantial clinical data. Studies validated its reliability in distinguishing GH-deficient patients from normal subjects, with standardized 100 mcg IV bolus protocols producing well-characterized dose-response curves across pediatric and adult populations. **Body Composition Research**: Clinical investigations have demonstrated that repeated GHRP-2 administration over weeks to months produces sustained elevations in IGF-1 and measurable improvements in lean body mass. Studies in elderly and GH-deficient populations have shown increased muscle protein synthesis rates and preferential fat mass reduction. **Appetite and Metabolic Regulation**: While GHRP-2 stimulates appetite through ghrelin receptor activation, research indicates the orexigenic effect is approximately 40-50% less intense than GHRP-6 at equivalent GH-releasing doses. This has made GHRP-2 a preferred option in protocols where appetite stimulation is undesirable. **Cardioprotective and Cytoprotective Studies**: Preclinical research in ischemia-reperfusion models has shown that GHRP-2 reduces myocardial infarct size and preserves hepatic function through antioxidant and anti-apoptotic mechanisms. These effects appear to involve CD36-mediated pathways and are independent of GH release.

Research protocols for GHRP-2 are well-defined from clinical pharmacology studies: **Typical Research Doses**: Subcutaneous doses of 100-300 mcg per administration are standard in research protocols. The GH response saturates at approximately 100-200 mcg (or ~1-2 mcg/kg), with diminishing additional benefit at higher doses. The approved diagnostic dose in Japan is 100 mcg administered as a single IV bolus. **Administration and Timing**: Subcutaneous injection on an empty stomach is the standard research route. Protocols commonly employ 2-3 daily injections (morning, post-exercise, and before sleep) to capitalize on physiological GH pulse windows. A minimum 30-minute fast before and after injection is recommended to avoid blunting the GH response. **Combination Protocols**: GHRP-2 is frequently paired with GHRH analogs such as Sermorelin or CJC-1295 (without DAC) at 1:1 microgram ratios. This combination exploits the synergistic GH-releasing interaction between the GHRP and GHRH pathways and represents the most common multi-peptide design in GH secretagogue research. **Important Disclaimer**: GHRP-2 is available for research purposes only outside of its approved diagnostic application in Japan. All dosing parameters reflect published research literature and should not be interpreted as therapeutic recommendations. Appropriate institutional oversight is required for all research applications.

GHRP-2's safety profile is well-characterized from its approved diagnostic use and extensive research: **Observed Effects**: Common effects include increased appetite (less intense than GHRP-6), transient flushing, injection site reactions, headache, and dizziness. Dose-dependent elevations in cortisol and prolactin occur but are typically modest and self-limiting at standard doses. Water retention may be observed, particularly in the initial weeks of repeated administration. **Potential Concerns**: Sustained use may affect glucose metabolism through GH-mediated insulin antagonism. The cortisol and prolactin co-stimulation, while less than GHRP-6, remains more pronounced than with Ipamorelin. At higher doses (>300 mcg), cortisol and prolactin elevations become more significant and may be undesirable in certain research contexts. **Research Limitations**: Despite robust short-term pharmacology data from diagnostic use, long-term safety data for chronic GHRP-2 administration in humans is limited. Most repeated-dose studies span weeks to months rather than years. The long-term impact on insulin sensitivity, pituitary function, and cardiovascular parameters in diverse populations requires further investigation.