GHRP-2 (Pralmorelin, GPA-748, KP-102)
GHRP-2 is short for Growth Hormone Releasing Peptide 2, a growth hormone (GH) secretagogue. As its name suggests, this drug stimulates the release of growth hormone. GHRP-2 is presently available as a diagnostic drug for GH deficiency in some markets, where it is usually found under the generic name pralmorelin. GHRP-2 is a fairly potent stimulator of GH release. Though it only increases the body’s own synthesis of this hormone, given proper dosing it can produce strong supraphysiological levels of GH on par with exogenous hGH (Human Growth Hormone) administration. It can also be significantly more cost effective in comparison. GHRP-2 is most commonly used in the fitness community for the purposes of fat loss and muscle gain, as well as an anti-aging therapy.
This drug belongs to the Growth Hormone Releasing Peptides (GHRP) class. These are all synthetic compounds that mimic, to some degree, the effects of ghrelin, an endogenous gastrointestinal peptide hormone.1 Ghrelin is secreted by the stomach at times of fasting (when unfed). This hormone stimulates receptors in various tissues including the hypothalamus, pituitary, and other regions of the brain, the sympathetic nervous system, the stomach, heart, pancreas, liver, and intestines, and even adipose tissue. Ghrelin is most generally involved in the regulation of food intake, body composition, and glucose metabolism.2 Among other things, it has been shown to stimulate appetite, influence taste, modulate sleep, stimulate gastric motility, emptying, and acid secretion, promote lean body mass retention, improve cardiac output, reduce inflammation, increase plasma glucose levels, and alter peripheral insulin sensitivity.3
Ghrelin is an agonist of the growth hormone secretagogue receptor 1a (GHSR1a).4 As such, it has been shown to increase acute GH release and 24-hour pulsatile GH secretion from the anterior pituitary.5 6 This, in turn, may also support increases in IGF-1 (Insulin-like Growth Factor 1) production. Several other pituitary-secreted or linked hormones may also be stimulated in the elevated presence of ghrelin, including ACTH (adrenocorticotropic hormone), cortisol, and prolactin. On the other hand, ghrelin may serve to lower insulin secretion and suppress LH (luteinizing hormone). Of course, depending on the therapeutic need, not all of this is desired. As a drug, ghrelin could produce spillover effects in other areas. This spillover tendency is reduced in many of the GHRP analogs, however, which are often more selective in their actions.
GHRP-2 does have a tendency to moderately increase ACTH, cortisol, and prolactin levels.7 These would be regarded as spillover effects on other systems. However, it does still seem to display some selectivity. It is estimated to be between 2-3 times more potent at stimulating GH release than its most direct predecessor, GHRP-6.8 At the same time, the appetite-stimulating properties are markedly lower. Some increase in appetite is still reported by a majority of users, however.9 This just occurs less commonly, and tends to be less profound and shorter lasting when it does. GHRP-2 is also regarded as less effective for injury healing in comparison. This might be linked to a lower level of spillover effect toward cortisol.
• Mild/Moderate Increase in Appetite
• Strong Effect on GH
• Moderate Elevations in Cortisol
• Moderate Elevations in Prolactin
This agent has a fairly long history for a class of agents that is regarded as relatively new from an approval and sales perspective. GHRP-2 was discovered by Dr. C. Y. Bowers at Tulane University, and first disclosed back in 1993.10 Dr. Bowers is a prominent figure in the field of GH secretagogues, and is credited with discovering or providing key research on many of these compounds. Dr. Bowers partnered with Keken Pharmaceuticals to develop GHRP-2 as a drug product. After a series of clinical trials, the drug (as pralmorelin) gained approval in Japan for the diagnosis of growth hormone deficiency. It was launched in 2005 under the brand name GHRP Kaken 100 Injection.
In 2012, this agent was also granted orphan drug status in the United States for the same application, where it is marketed by Sella Pharmaceuticals. GHRP-2 has also been investigated in several clinical trials for the treatment of short stature in children. However, though early results seemed promising, no such product has yet been approved for this application.
GHRP-2 is on the World Anti-Doping Agency’s (WADA) list of prohibited substances. Screening for this drug began on a large scale during the 2014 Winter Olympics in Sochi. This drug is now specifically detectable, at least for a short window after use, during routine urine analysis. A blood sample is not required.
GHRP Kaken 100 Injection is supplied in a multi-dose vial containing a single 100 mcg dose. Compounded medicine and gray market versions typically contain 5 mg or 10 mg of dry lyophilized powder in a multi-dose vial. This is reconstituted with a diluent (sterile water or bacteriostatic water) before use
GHRP-2 is a synthetic hexapeptide with the chemical name Dalanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-Ltryptophyl-Dphenylalanyl-L-lysinamide hydrochloride, dihydrochloride. This is a short peptide chain, which is relatively stable. GHRP-2 has a halflife in serum of approximately 30 minutes.11 It displays a poor but viable level of bioavailability via oral administration (.3-1%). Intranasal bioavailability is high at 53%, though injection is the preferred route of administration.12 13
GHRP-2 should be used with care in epileptic patients. Obesity, uncontrolled hypothyroidism, hyperglycemia, or elevated plasma fatty acids may impair the effectiveness of GHRP-2. This drug should never be used during pregnancy, with cancer, a history of cancer, diabetic retinopathy, sclerosing diseases of the liver or lungs, intracranial hypertension, or uncontrolled diabetes.
Side Effects (General):
Common side effects to GHRP-2 therapy include flushing, sweating, sleepiness, increased GI motility, and increased appetite. Also frequently reported are adverse effects typically associated with other types of growth hormone therapy, such as water retention (edema), joint pain (arthralgias), carpal tunnel syndrome, and numbness or tingling in the extremities. Note that the incidence of side effects tends to be lower with GHRP therapy as compared to traditional hGH. This is because GH/IGF-1 release is subject to endogenous synthesis, and as such the drug is less amenable to overdosing
Side Effects (Injection site):
The subcutaneous administration of this drug may cause redness, itching, pain, or lumps at the site of injection. Injection site redness and discomfort is sometimes reported with intramuscular injection as well.
Side Effects (Impaired glucose tolerance):
GHRP-2 may reduce insulin sensitivity and raise blood sugar levels. This may occur in individuals without preexisting diabetes or impaired glucose tolerance.
GHRP-2 may be given orally, via intranasal administration, subcutaneous (SC) injection, or intramuscular (IM) injection. However, given its high cost and lower bioavailability via other routes, injection is used almost exclusively.
When used for physique- or performance-enhancing purposes, GHRP2 is usually administered at a dosage of 0.1 to 0.3 mg (100-300 mcg) per injection. This may be given 1-3 times daily. If single episode dosing is preferred, this is taken before sleep. Day dose(s) are taken on an empty stomach, 30-60 minutes before feeding. This is to preserve optimal GH release, as elevated plasma fatty acids and/or glucose may blunt the GH elevating effects of GHRP-2. Total daily dosage generally does not exceed 900 mcg.
It is common to taper up the dosage, beginning with 100 mcg per injection. The dosage may then be increased in increments of 50 mcg every 3-7 days, until a stable dosage is reached.
Cycles of GHRP-2 usually last 3-4 months in length, though programs of 6 months or longer are not uncommon. Although desensitization to GHRPs may occur over time, this drug appears to maintain an acceptable level of effectiveness during longer cycles.
Drugs of the GHRP class are often combined with those of the GHRH (Growth Hormone Releasing Hormone) category, such as sermorelin or CJC-1295. These two drug types alter GH release through two distinct and complimentary mechanisms. Such combination therapy produces substantial synergy with regard to GH release, producing maximum GH elevations that are unobtainable with either drug alone.14 Note that injections of GHRP-2 are typically reduced to no more than 200 mcg each during combination therapy, and 600 mcg total per day.
Below is an example of combination therapy with GHRP-2
GHRP-2 is available as a prescription drug product under the brand name GHRP Kaken 100 Injection. It is also widely available in the United States as a compounded medicine, and is often offered at anti-aging and hormone replacement clinics. Lastly, the drug is widely sold as a gray market ‘research compound’ as well, though the quality of gray market GHRP-2 products can be difficult to assure.
1 Ghrelin is a growth-hormone-releasing acylated peptide from the stomach. Kojim M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Nature. 1999; 402(6762):656-660.
2 Ghrelin induces adiposity in rodents. M. Tschop, D.L. Smiley, M.L. Heiman. Nature, 407 (2000), pp. 908-913
3 Ghrelin.T.D. Müller1, R. Nogueiras et al. Molecular Metabolism. Volume 4, Issue 6, June 2015, Pages 437-460
4 Physiology of ghrelin and related peptides. L. L. Anderson, S. Jeftinija, C. G. Scanes, M. H. Stromer, J. S. Lee, K. Jeftinija, A. Glavaski-Joksimovic. Domest. Anim. Endocrinol. 2005, 29, 111.
5 Ghrelin is a growth-hormone-releasing acylated peptide from stomach. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, K. Kangawa. Nature, 402 (1999), pp. 656-660
6 Twenty-four hour continuous ghrelin infusion augments physiologically pulsatile, nycthemeral, and entropic (feedbackregulated) modes of growth hormone secretion. J.D. Veldhuis, G.A. Reynolds, A. Iranmanesh, C.Y. Bowers et al. The Journal of Clinical Endocrinology and Metabolism, 93 (2008), pp. 3597–3603
7 Effects of GHRP-2 and hexarelin, two synthetic GH-releasing peptides, on GH, prolactin, ACTH and cortisol levels in man. Comparison with the effects of GHRH, TRH and hCRH. Arvat, E., et al. Peptides, 1997. 18(6): pp. 885-91
8 Characterization of Growth Hormone Secretion to Growth Hormonereleasing Peptide-2 in Domestic Animals – A Review. Sang-Gun Roh, Hong-Gu Lee et al. Asian-Aust. J. Anim. Sci. 2002. Vol 15, No.5:757 -766.
9 Growth Hormone Releasing Peptide -2 (GHRP-2), like ghrelin, increases food intake in healthy men Blandine Laferrère, Cynthia Abraham, Colleen D. Russell, and Cyril Y. Bowers 2010
10 Bowers, C. Y. GH releasing peptides. Structure and kinetics. J. Pediatr. Endocrinol. 6:21-31; 1993.
11 Effect of newly developed analogue of growth hormone releasing peptide [D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102)] on growth hormone secretion in adult male rats. Sawada H. Nihon Ika Daigaku Zasshi. 1995;62(2):142–149.
12 Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption. P.B. JOHANSEN et al. Xenobiotica, 1998 V.28 N. 11.1083-92
13 Effects of eight months treatment with graded doses of a growth hormone (GH)-releasing peptide in GH-deficient children. Merica V, Cassorla F, Salazar T, Avila A, Iñiguez G, Bowers CY, Merriam GR. 1998
14 Determinants of GH-releasing hormone and GH-releasing peptide synergy in men. Veldhuis JD, Bowers CY.. Am J Physiol Endocrinol Metab. 2009 May;296(5):E1085-92