GHRP-2

GHRP-2, also known as pralmorelin or KP-102, is a synthetic hexapeptide with the sequence D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH2 and a molecular weight of approximately 818 Da. It belongs to the growth hormone releasing peptide (GHRP) family, a class of synthetic compounds that stimulate GH secretion through a pathway entirely distinct from GHRH. The presence of two D-amino acids (D-Ala and D-Phe) and a non-natural amino acid (D-beta-naphthylalanine) confers resistance to enzymatic degradation and gives the peptide its characteristic receptor selectivity.

GHRP-2 acts as a potent agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a), the endogenous receptor for ghrelin. However, GHRP-2 is considerably more selective for GH release than ghrelin itself, producing less pronounced appetite stimulation and minimal effects on cortisol and prolactin at standard doses. The GHS-R1a is expressed on both hypothalamic neurons and pituitary somatotrophs. At the hypothalamic level, GHRP-2 suppresses somatostatin release from periventricular neurons and stimulates GHRH-releasing neurons in the arcuate nucleus. At the pituitary level, it directly amplifies the amplitude of GH secretory pulses by activating phospholipase C and raising intracellular calcium in somatotroph cells.

The synergy between GHRP-2 and GHRH analogs is one of the most well-documented phenomena in GH secretagogue research. A study published in the Journal of Clinical Endocrinology and Metabolism by Bowers et al. demonstrated that co-administration of GHRP-2 with GHRH produced a GH response approximately 3 times greater than GHRH alone and 2 times greater than GHRP-2 alone. This synergy occurs because the two classes of secretagogues act through complementary mechanisms: GHRH drives GH synthesis and release via cAMP, while GHRP-2 removes the somatostatin brake and amplifies pulse amplitude via the PLC/calcium pathway.

In clinical pharmacology studies, GHRP-2 administered intravenously at 1 mcg/kg increased peak GH levels 7-15 fold above baseline within 15-30 minutes. Subcutaneous administration produces a slightly delayed but still robust response, with peak GH occurring at 30-45 minutes. The plasma half-life of GHRP-2 is approximately 25-30 minutes, and the GH-releasing effect persists for approximately 2-3 hours per dose.

GHRP-2 has been approved in Japan under the brand name Pralmorelin (manufactured by Kaken Pharmaceutical) as a diagnostic agent for growth hormone deficiency. In the diagnostic protocol, 100 mcg is administered intravenously and GH is sampled at 15, 30, 45, and 60 minutes. A peak GH response below 9 ng/mL is considered indicative of severe GH deficiency. This regulatory approval confirms the peptide's well-characterized safety and pharmacology in human subjects.

Beyond GH release, GHRP-2 has demonstrated cytoprotective properties in preclinical models. Studies published in Life Sciences and the Journal of Molecular and Cellular Cardiology showed that GHRP-2 reduced infarct size in ischemia-reperfusion models of myocardial injury and protected hepatocytes from oxidative damage. These effects appear to be mediated through GHS-R1a-dependent activation of PI3K/Akt survival signaling, independent of GH elevation.

For reconstitution, lyophilized GHRP-2 should be reconstituted with bacteriostatic water or sterile water. The reconstituted solution should be stored at 2-8 degrees C and used within 21 days. Lyophilized powder is stable at room temperature for short periods but should be stored at -20 degrees C for long-term preservation. GHRP-2 is generally stable in solution at physiological pH (7.0-7.5).

The safety profile of GHRP-2 in published human studies is favorable. The most commonly reported effects are transient facial flushing and a mild increase in appetite lasting 30-60 minutes post-dose. At standard doses (100-300 mcg SC), GHRP-2 does not produce clinically significant elevations in cortisol or prolactin, distinguishing it from earlier GH secretagogues like hexarelin. Repeated dosing studies over 6-12 weeks show maintained GH responsiveness without significant tachyphylaxis.