GHRP-6, GHRP-2, hexarelin, and ipamorelin are synthetic ghrelin-receptor (GHSR) ligands. They are not GHRH analogs. They are not four doses of one hexapeptide.
This page is a class comparison. The pairwise GHRP-2 versus GHRP-6 receptor and second-messenger data live on GHRP-2 vs GHRP-6. Ipamorelin versus a GHRH analog lives on Ipamorelin vs CJC-1295. What is missing from those pair pages, and is the search intent here, is hexarelin plus ACTH/cortisol/PRL selectivity across the GHSR series.
Research notice: These peptides are discussed for laboratory research only. They are not approved for human consumption, medical treatment, or diagnosis.
| Parameter | GHRP-6 | GHRP-2 | Hexarelin | Ipamorelin |
|---|---|---|---|---|
| Class | Hexapeptide GHRP | Hexapeptide GHRP | Hexapeptide GHRP (2-methyl-Trp analog) | Pentapeptide GHRP-class secretagogue |
| Published sequence notes | His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (Bowers 1990) | Hexapeptide analog in the same series | His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2 (Deghenghi; Imbimbo) | Aib-His-D-2-Nal-D-Phe-Lys-NH2 (Raun) |
| Receptor family | GHSR / GHRP-like | GHSR / GHRP-like | GHSR / GHRP-like | GHSR / GHRP-like |
| Human GH | Bowers 1990 men, synergy with GHRH | Same class; Arvat 1997 vs hexarelin | Ghigo 1994 routes; Imbimbo 1994 dose-response | Gobburu 1999 IV PK/PD |
| ACTH/cortisol | Raised in swine (Raun); ~2-fold cortisol at highest IV dose in Bowers men | Raised in swine (Raun); similar to hexarelin in Arvat men | Dose-related in Massoud men; similar to CRH in Ghigo 1997 healthy subjects | Not above GHRH-like levels in Raun swine |
| Human food intake RCT cited | Not cited here | Laferrere 2005, 2006 | Not cited here | Not cited here |
| FDA-approved product | No | No | No | No |
Howard et al. cloned a pituitary and hypothalamus receptor that functions in GH release. Kojima et al. identified ghrelin as the endogenous acylated GH-releasing peptide from stomach.
GHRP-6 is the hexapeptide Bowers et al. used to show GH release in 18 normal men and synergy with GHRH-(1-44)-NH2.
GHRP-2 is a later hexapeptide in the same chemical class. Cheng et al. (PMID 9096259) concluded that, in rat primary pituitary cells, GHRP-2 and GHRP-6 share receptor and mechanism: no additive GH at maximal concentrations, cross-desensitization, GHRP antagonist block. Wu et al. (PMID 8699133) showed species splits on cAMP. That pairwise detail is on GHRP-2 vs GHRP-6, not repeated here.
Hexarelin substitutes 2-methyl-Trp into the GHRP-6 backbone. Deghenghi et al. reported GH-releasing activity in infant and adult rats, similar to GHRP-6 after IV doses, slightly more effective after subcutaneous administration in that model.
Ipamorelin was characterized by Raun et al. as the first selective GH secretagogue in its series. In rat pituitary cells it released GH with potency similar to GHRP-6. GHRP and GHRH antagonists showed it acts via a GHRP-like receptor, not by mimicking GHRH.
They compete at the same receptor family. Cheng's rat-cell result (no additive max effect of GHRP-2 plus GHRP-6) is a reason not to treat two GHRPs as independent GH channels. It is a cell-system result, not a human stacking protocol.
None of the four is an FDA-approved drug in the sources cited. Human papers below are healthy-volunteer GH-release, ACTH/cortisol/PRL, PK/PD, or (for GHRP-2) food-intake pharmacology.
IV bolus GHRP (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) in 18 normal men, alone and with GHRH. Mean peak serum GH after placebo and three GHRP dose levels was 1.2, 7.6, 16.5, and 68.7 micrograms/L. Submaximal GHRP plus GHRH stimulated GH synergistically. At the highest GHRP dose, serum PRL and cortisol rose about 2-fold; LH and TSH did not change over the first hour.
Those IV amounts are trial methods, not a use protocol.
Laferrere, Abraham, Russell et al. (2005) reported that GHRP-2, like ghrelin, increased food intake in healthy men. Laferrere, Hart, and Bowers (2006) reported that obese subjects also increased food intake after GHRP-2. That is GHRP-2, not a verified GHRP-6, hexarelin, or ipamorelin human meal RCT in the sources below.
Ghigo et al. (1994) gave hexarelin IV, subcutaneous, intranasal, and oral to 12 healthy young volunteers versus saline and GHRH 1 microgram/kg IV. GH AUC after 1 microgram/kg IV hexarelin was about twice GHRH at the same IV amount (3175 versus 1544 micrograms/min.L). Subcutaneous bioavailability versus IV was 77.0%. Intranasal 4.8%. Oral 0.3%.
Imbimbo et al. (1994) gave IV hexarelin 0.5, 1, and 2 micrograms/kg to 12 healthy men. GH peaked at about 30 minutes and returned toward baseline within 240 minutes; they reported a GH half-life of about 55 minutes after those peaks. That is the GH decay, not a measured hexarelin plasma half-life.
Massoud, Hindmarsh, and Brook (1996) constructed IV hexarelin dose-response curves in healthy adult men. GH ED50 was 0.48 microgram/kg. PRL rose with dose (plateau about 180% of baseline; ED50 0.39 microgram/kg). Cortisol showed a step increase of about 40% at 0.5 microgram/kg. Low-dose hexarelin (0.125 microgram/kg) plus GHRH-(1-29)-NH2 (1.0 microgram/kg) produced large GH release with a moderate PRL rise and no cortisol rise in that experiment.
Ghigo, Arvat, Ramunni et al. (1997) compared hexarelin 2.0 micrograms/kg IV with human CRH in healthy subjects and in Cushing syndrome. In healthy subjects, hexarelin raised ACTH (peak 32.4 versus baseline 16.3 pg/mL) and cortisol (135.9 versus 110.0 micrograms/L), similar to CRH. In Cushing disease the hexarelin ACTH/cortisol responses were larger than CRH. In adrenal or ectopic Cushing, neither peptide changed ACTH or cortisol.
In six young adults, 1 and 2 micrograms/kg IV GHRP-2 and hexarelin produced similar strong GH responses, both higher than GHRH 1 microgram/kg. PRL, ACTH, and cortisol also rose; PRL rises were lower than after TRH, and ACTH/cortisol rises were similar to CRH. The authors concluded GHRP-2 and hexarelin are not fully GH-specific. In six elderly subjects, GH responses to 2 micrograms/kg of either peptide were lower than in the young.
Raun et al.: rat pituitary, anesthetized rats, and conscious swine. GH comparable to GHRP-6. In swine, GHRP-6 and GHRP-2 raised ACTH and cortisol; ipamorelin did not above GHRH-like levels. FSH, LH, prolactin, and TSH were unchanged for the secretagogues tested.
Gobburu et al. infused ipamorelin over 15 minutes in healthy men. Terminal half-life 2 hours. GH showed a single episode peaking at 0.67 hours. SC50 214 nmol/L. Infusion rates are study methods, not a protocol.
| Question | GHRP-6 | GHRP-2 | Hexarelin | Ipamorelin |
|---|---|---|---|---|
| GHSR class | Yes | Yes | Yes | Yes |
| Human GH + GHRH synergy cited | Bowers 1990 men | Same class; Cheng synergy with GRF in rat cells | Massoud: low-dose hexarelin plus GHRH-(1-29) | Not the Gobburu design |
| Human ACTH/cortisol | Bowers highest IV dose ~2-fold cortisol; Raun swine increase | Arvat similar to hexarelin; Raun swine increase | Massoud dose-related; Ghigo similar to CRH in healthy subjects | Selective in Raun swine |
| Human food-intake RCT cited | No | Yes (Laferrere) | No | No |
| Human PK half-life cited | Not cited | Not cited | GH decay ~55 min after IV (Imbimbo); not peptide t1/2 | 2 hours terminal (Gobburu IV) |
If the experimental variable is GHSR occupancy with published human ACTH/cortisol curves, hexarelin and GHRP-2 have those human papers. If the variable is ACTH/cortisol dissociation versus GHRP-6/GHRP-2, ipamorelin is the ligand Raun isolated in swine. If the variable is human meal intake, GHRP-2 is the peptide with the Laferrere trials.
Related: GHRP-2 vs GHRP-6, Ipamorelin vs CJC-1295.
No. The pairwise rat-pituitary, cAMP, and GHRP-2 food-intake comparison is GHRP-2 vs GHRP-6. This page is the GHSR class: hexarelin (not on that pair page), ipamorelin selectivity, and ACTH/cortisol/PRL signals across the series.
No. Howard et al. cloned the pituitary/hypothalamus receptor this class uses. Kojima et al. identified ghrelin as the endogenous ligand. GHRH analogs act at the GHRH receptor. See Ipamorelin vs CJC-1295 for that split.
In swine, Raun et al. found GHRP-6 and GHRP-2 raised ACTH and cortisol. Ipamorelin did not raise ACTH or cortisol above GHRH-like levels, including at doses more than 200-fold the GH ED50 in that model. That is swine pharmacology, not a human safety label.
No. Massoud et al. showed dose-dependent GH, PRL, and cortisol after IV hexarelin in healthy men. Arvat et al. found GHRP-2 and hexarelin produced similar GH responses and similar PRL, ACTH, and cortisol increases in young adults. Ghigo et al. found hexarelin ACTH/cortisol responses similar to CRH in healthy subjects.
No. It compares published research. It is not medical advice and does not include human dosing protocols.
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