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Hexarelin

From PeptidePlaza, the free peptide reference · Entry #015 · Anti-Aging · Hand-curated entry · Editorial standards

Research warning. For educational reference only. Cortisol and prolactin elevation may be undesirable in many research contexts. Not suitable for protocols requiring isolated GH evaluation.

Hexarelin (also known as Examorelin, GHRP-His-D2Nal) is a anti-aging research peptide. A potent six-amino acid growth hormone secretagogue. Among the strongest GHRPs studied, but notable for also elevating cortisol and prolactin — making it useful for studying GH axis effects with concurrent stress-hormone activation.

Hexarelin is a synthetic hexapeptide growth hormone secretagogue (GHS) and one of the most potent GHSR-1a agonists studied. It produces significantly greater GH release than GHRP-2 or GHRP-6 at equivalent doses. Unlike the highly selective Ipamorelin, Hexarelin also activates ACTH/cortisol and prolactin pathways. Research has also identified cardioprotective effects independent of GH — Hexarelin binds CD36 receptors in cardiac tissue, reducing ischemic damage. This dual GHS/cardiac receptor activity makes it a unique research compound.

1 Mechanism of action

Potent GHSR-1a agonism drives GH release; also activates ACTH, cortisol, and prolactin pathways (non-selective). Separate cardioprotective mechanism via CD36 receptor binding in myocardial tissue — GH-independent.

Primary targets: GHSR-1a · CD36 (cardiac) · ACTH/cortisol axis

2 Reported effects

Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.

2.1 Reported benefits

  • Most potent GH secretagogue among GHRPs studied
  • Cardioprotective effects via CD36 receptor (GH-independent)
  • Strong appetite stimulation for anabolic research protocols

2.2 Side effects

  • Cortisol and prolactin elevation (non-selective HPA axis activation)
  • Water retention and mild edema
  • Appetite increase (ghrelin receptor activation)

3 Chemical and physical properties

CAS number140703-51-1
Molar mass887.05 g/mol
Purity (typical)>99.3%
Half-life~1–2 hours
Storage−20 °C, lyophilised powder, desiccated
SolubilitySterile water / bacteriostatic water
Receptors / targetsGHSR-1a, CD36 (cardiac), ACTH/cortisol axis

3.1 Amino acid sequence

His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH₂

4 Research dosages

1–3 μg/kg SC 2–3 times daily in research protocols; 100–300 μg per dose range.

Dosages are reported from published protocols for reference only. Research chemicals are not for human consumption.

5 Research studies (8)

  1. Hexarelin: A Growth Hormone Secretagogue with Cardioprotective Properties
    Endocrinology (2003) · Preclinical · N=60 (rats)
    Identified CD36 as a Hexarelin receptor in cardiac tissue. Hexarelin reduced ischemic damage in isolated rat hearts independent of GH release.
    Key finding: Hexarelin binds CD36 in cardiac tissue — reducing infarct size by 30–40% via a GH-independent mechanism.
  2. Comparison of GH Secretion After GHRP-6, GHRP-2 and Hexarelin
    Journal of Clinical Endocrinology & Metabolism (1997) · RCT · N=12
    Hexarelin produced the greatest GH peak of all peptides tested, but with corresponding elevations in cortisol and prolactin unlike selective GHSRs.
    Key finding: Hexarelin = strongest GH release; highest cortisol (+87%) and prolactin (+245%) co-elevation — least selective GHSR tested.
  3. Hexarelin promotes the survival of retinal ganglion cells after optic nerve transection
    Indian journal of pharmacology (2026) · Preclinical
    Single daily doses of hexarelin dose dependently increased the survival of RGC.
  4. Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway
    European journal of medical research (2023) · Preclinical
    Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.
  5. Protective Effects of Hexarelin and JMV2894 in a Human Neuroblastoma Cell Line Expressing the SOD1-G93A Mutated Protein
    International journal of molecular sciences (2023) · Review
    Further investigations are required for the following: (i) to clarify GHS molecular mechanisms of action, and (ii) to envisage the development of new GHSs that may be useful in ALS therapy.
  6. Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models
    Frontiers in physiology (2021) · Preclinical
    PMCID: PMC8814524 PMID: 35126171 The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
  7. Hexarelin modulates lung mechanics, inflammation, and fibrosis in acute lung injury
    Drug target insights (2021) · Preclinical
    Our data suggest that hexarelin can inhibit the early phase of the inflammatory response in a murine model of HCl-induced ARDS, thereby blunting lung remodeling processes and fibrotic development.
  8. Hexarelin attenuates abdominal aortic aneurysm formation by inhibiting SMC phenotype switch and inflammasome activation
    Microvascular research (2022) · Preclinical
    These results demonstrated that hexarelin attenuated AAA development by inhibiting SMC phenotype switch and NF-κB signaling mediated inflammatory response.

6 Safety and risk profile

6.1 Regulatory status

Hexarelin is currently classified as Phase 2 clinical trials. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.

Safety score: 42/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.

6.2 Contraindications

Conditions and populations in which use is contraindicated:

  • Cushing syndrome or hypercortisolism
  • Hyperprolactinemia or prolactinoma
  • Active malignancy (IGF-1 concern)
  • Uncontrolled diabetes

6.3 Drug interactions

Drug or classInteractionRisk
CorticosteroidsAdditive HPA axis activation — risk of excessive cortisol effects.High
Dopamine agonists (bromocriptine, cabergoline)May counteract Hexarelin-induced prolactin elevation.Low

6.4 Long-term risks

  • Chronic cortisol elevation and associated metabolic effects
  • Prolactin-related effects (galactorrhea, libido changes)
  • Pituitary receptor desensitization
  • Hypothalamic-pituitary axis disruption with prolonged use

6.5 Research best practices

  • Store at −20 °C; avoid moisture
  • Administer fasted for optimal GH response
  • Rotate injection sites to prevent lipoatrophy
  • Consider cycling (3–5 days on / 2 days off) to mitigate cortisol effects
Safety data disclaimer. Safety assessments are based on published literature and are for educational reference only. Clinical evidence varies significantly between peptides. Always consult primary research and current regulatory guidance.

7 Frequently asked questions

Why would researchers choose Hexarelin over Ipamorelin?
Hexarelin is chosen when studying the combined GH + cortisol + prolactin axis, or when exploring its unique CD36-mediated cardioprotective effects. Ipamorelin is preferred for isolated GH axis research without stress hormone interference.
What are the cardiprotective effects of Hexarelin?
Independent of GH release, Hexarelin binds the CD36 scavenger receptor on cardiac cells, reducing damage from ischemia-reperfusion injury by 30–40% in animal models. This dual mechanism makes it unique among GHSRs.

8 References

  1. Hexarelin promotes the survival of retinal ganglion cells after optic nerve transection PubMed (2026). Chow KBS, et al.. View source
  2. Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway PubMed (2023). Guan C, et al.. View source
  3. Protective Effects of Hexarelin and JMV2894 in a Human Neuroblastoma Cell Line Expressing the SOD1-G93A Mutated Protein PubMed (2023). Meanti R, et al.. View source
  4. Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models PubMed (2021). Waddingham MT, et al.. View source

Related compounds

Entries that share a target, a mechanism, or a research area with Hexarelin.

GHRP-2anti-aging

Also targets GHSR-1a

A second-generation synthetic hexapeptide GHRP and potent GHSR-1a agonist. More selective than GHRP-6 with less ghrelin-like appetite stimulation, making it widely used in GH axis research protocols.

Ipamorelinanti-aging

Also targets GHSR-1a

A pentapeptide ghrelin mimetic renowned for its exceptional receptor selectivity. Unlike other GHSRs, Ipamorelin does not significantly raise cortisol, ACTH, or prolactin — making it a clean research tool for isolated GH axis studies.

AOD-9604metabolic

Shares activates and release pharmacology

A modified C-terminal fragment of human growth hormone (amino acids 177-191) with a tyrosine substitution. Studied primarily for its lipolytic (fat-burning) effects without the growth-promoting activity of full-length hGH.

CJC-1295anti-aging

Shares activates and release pharmacology

A tetrasubstituted GHRH analog with four amino acid substitutions that increase receptor affinity and proteolytic resistance. Most commonly studied in combination with Ipamorelin for synergistic GH pulse amplification.

Semaxnootropic

Shares activates and cortisol pharmacology

A synthetic analog of a fragment of ACTH that lacks hormonal activity but retains potent neuroprotective and cognitive-enhancing properties. Widely used in Russian clinical settings for stroke, memory, and attention disorders.

Humaninanti-aging

Shares activates and pathways pharmacology

A 21-amino acid mitochondria-encoded peptide discovered through its ability to rescue neurons from Alzheimer's-related death. Like MOTS-c, it belongs to the emerging class of mitochondrial-derived peptides with systemic metabolic and cytoprotective effects.

9 See also

For research reference only. Not medical advice. Peptides may be regulated or restricted in your jurisdiction. Entry validated by the PeptidePlaza Biomedical Research Desk; see editorial standards.

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