Ipamorelin

Overview

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue originally developed by Novo Nordisk in the late 1990s. It was identified through systematic structure-activity relationship studies aimed at producing a GH-releasing compound with improved selectivity over earlier growth hormone-releasing peptides (GHRPs) such as GHRP-6 and GHRP-2 [1].

The compound's distinguishing characteristic is its selectivity for GH release. In animal studies conducted by Raun et al., ipamorelin stimulated GH secretion with potency comparable to GHRP-6 but did not produce significant increases in adrenocorticotropic hormone (ACTH), cortisol, or prolactin at effective GH-releasing doses [1]. This selectivity profile differentiates ipamorelin from most other peptide and non-peptide GH secretagogues, which typically activate multiple neuroendocrine pathways at therapeutic doses [4].

Ipamorelin has been investigated in Phase II clinical trials for post-surgical gastrointestinal recovery but has not received regulatory approval for any indication [5]. It remains classified as an investigational compound.

Mechanism of Action

Ipamorelin exerts its effects primarily through activation of the growth hormone secretagogue receptor type 1a (GHS-R1a), also known as the ghrelin receptor [1][3].

GHS-R1a Activation: Ipamorelin binds to GHS-R1a on somatotroph cells of the anterior pituitary, stimulating GH release through a phospholipase C-dependent intracellular calcium signaling pathway. This mechanism is distinct from and complementary to the cAMP-dependent pathway used by GHRH [3].

Selectivity Profile: The selectivity of ipamorelin has been characterized through dose-response studies comparing its effects on GH, ACTH, cortisol, and prolactin. In the foundational study by Raun et al. (1998), ipamorelin released GH with an ED50 comparable to GHRP-6 in swine, but did not affect ACTH or cortisol levels even at doses up to 200-fold above the GH-releasing ED50 [1]. By comparison, GHRP-6 and GHRP-2 elevated cortisol and ACTH at or near their GH-effective doses [1][4].

Comparison to Other GH Secretagogues:

| Compound | GH Release | Cortisol Elevation | Prolactin Elevation | ACTH Elevation | |---|---|---|---|---| | Ipamorelin | Yes | Minimal [1] | Minimal [1] | Minimal [1] | | GHRP-6 | Yes | Yes [4] | Yes [4] | Yes [4] | | GHRP-2 | Yes | Moderate [4] | Moderate [4] | Moderate [4] | | MK-677 (oral) | Yes | Transient [6] | Variable [6] | Variable [6] |

Pulsatile GH Release: Like other GHS-R1a agonists, ipamorelin amplifies pulsatile GH secretion rather than producing a tonic elevation. Pharmacokinetic-pharmacodynamic modeling by Gobburu et al. demonstrated that the GH response to ipamorelin follows a rapid-onset, short-duration pulse consistent with physiological secretory patterns [2].

Pharmacokinetics

The pharmacokinetic properties of ipamorelin have been characterized in human volunteers and animal models through PK-PD modeling studies [2].

Absorption

Following subcutaneous injection, ipamorelin is absorbed rapidly into the systemic circulation. Time to peak plasma concentration (Tmax) occurs within approximately 15-30 minutes after SC administration [2]. The subcutaneous bioavailability of small peptides in this molecular weight range (711.85 Da) is generally high, estimated at 65-95%, as molecules of this size pass readily through subcutaneous capillary fenestrations with minimal local degradation [2][10].

After intravenous administration of 1 μg/kg, ipamorelin produced measurable GH peaks within 15-20 minutes, confirming rapid distribution to pituitary target tissues [2].

Distribution

Gobburu et al. (1999) characterized the pharmacokinetics of ipamorelin using a two-compartment model in healthy male volunteers. The volume of distribution at steady state was estimated at approximately 0.2-0.4 L/kg, consistent with a hydrophilic peptide that distributes primarily into the extracellular fluid compartment with limited tissue penetration [2]. Protein binding has not been precisely quantified for ipamorelin but is expected to be low to moderate based on the physicochemical properties of the pentapeptide structure.

Metabolism and Elimination

Ipamorelin is metabolized primarily through enzymatic degradation by ubiquitous peptidases, including dipeptidyl peptidase-IV (DPP-IV), aminopeptidases, and carboxypeptidases present in plasma, liver, and kidney [2][10]. The modified N-terminal aminoisobutyric acid (Aib) residue and the D-amino acid substitutions (D-2-naphthylalanine, D-phenylalanine) confer partial resistance to peptidase degradation compared to endogenous peptides, contributing to the extended half-life relative to native ghrelin [1][10].

The terminal elimination half-life is approximately 2 hours in humans, as determined by PK-PD modeling [2]. This is substantially longer than the parent compound GHRP-6, which has a distribution half-life of approximately 7.6 minutes and an elimination half-life of approximately 2.5 hours after IV administration. Renal clearance contributes to elimination of intact peptide and metabolic fragments, though specific renal clearance values have not been published.

PK-PD Relationship

Gobburu et al. applied an indirect-response pharmacodynamic model to characterize the relationship between ipamorelin plasma concentration and GH release. The model demonstrated that GH secretion follows a sigmoid Emax function with respect to ipamorelin concentration, with rapid onset (peak GH at 30-60 minutes post-dose) and return to baseline within 2-3 hours [2]. The GH response was dose-proportional at lower doses and exhibited saturation kinetics at higher doses, consistent with a receptor-mediated mechanism [2].

Dose-Response Relationship

GH Release Across Dose Ranges

The dose-response relationship for ipamorelin-induced GH release has been characterized in both animal and human studies. In the Raun et al. (1998) swine model, the dose-response curve for GH release was assessed across a range of 0.01-0.1 mg/kg [1]:

| Dose (mg/kg) | Approximate GH Response | Cortisol Change | ACTH Change | |---|---|---|---| | 0.01 | Threshold GH release | None | None | | 0.03 | Moderate GH release | None | None | | 0.1 | Near-maximal GH release | None | None | | 1.0 (100x GH ED50) | Maximal GH plateau | None | None | | 2.0 (200x GH ED50) | At ceiling | None | None |

This dose-response profile is the defining pharmacological feature of ipamorelin: even at doses 200-fold above the ED50 for GH release, cortisol and ACTH levels remained at baseline [1]. This contrasts sharply with GHRP-6, where cortisol and ACTH elevation begins at or near the GH-effective dose range.

Human GH Response Data

In healthy human volunteers receiving intravenous ipamorelin at 1 μg/kg [2]:

• Peak GH timing: 30-60 minutes post-injection
• GH peak magnitude: Dose-dependent, comparable in amplitude to GHRP-6 at equivalent doses
• Duration of GH pulse: GH returned to baseline within 2-3 hours
• Reproducibility: GH response was consistent across repeated administrations in the same subjects

In the Beck et al. (2014) clinical trial using 0.03 mg/kg IV every 8 hours, repeated dosing over up to 7 days produced sustained GH pulses without evidence of acute tachyphylaxis at this dose and frequency [5].

Saturation Kinetics

The GH dose-response curve for ipamorelin follows sigmoid Emax kinetics, reaching a plateau at approximately 0.1 mg/kg in animal models [1][2]. Above this dose, further increases in ipamorelin concentration do not produce proportionally greater GH release, consistent with receptor saturation at the pituitary somatotroph level. Importantly, unlike GHRP-6 and hexarelin, increasing the dose above the GH saturation point does not "spill over" into activation of cortisol, ACTH, or prolactin secretion [1].

Safety and Hormonal Selectivity

The Key Differentiator: Hormonal Selectivity

The most clinically significant safety feature of ipamorelin is its selective activation of GH release without concomitant stimulation of cortisol, ACTH, or prolactin. This property has been documented across multiple studies and represents the primary pharmacological advantage over earlier GH secretagogues.

Raun et al. (1998) -- Foundational Selectivity Data [1]:

In the pivotal animal study using pentobarbital-anesthetized swine:

• GH release: ED50 comparable to GHRP-6 (both compounds produced equivalent maximal GH stimulation)
• ACTH: No increase at any dose tested, including doses 200-fold above the GH ED50. By contrast, GHRP-6 elevated ACTH at doses at or near the GH-effective dose
• Cortisol: No significant change even at the highest doses tested. GHRP-6 produced dose-dependent cortisol elevation beginning at GH-effective doses
• Prolactin: No significant elevation. GHRP-6 increased prolactin at GH-effective doses
• Aldosterone: No effect on aldosterone levels (GHRP-6 elevated aldosterone at higher doses)
• FSH and LH: No effect on gonadotropin levels

Comparison of hormonal specificity ratios (ACTH/GH ED50 ratios) [1]:

• Ipamorelin: ACTH ED50 was greater than 200-fold above GH ED50 (ACTH was not released at any dose tested)
• GHRP-6: ACTH ED50 was approximately 2-4-fold above GH ED50
• GHRP-2: ACTH ED50 was approximately 5-20-fold above GH ED50
• Hexarelin: ACTH and cortisol elevation occurred at approximately 40% of the maximal GH-releasing dose [15]

Arvat et al. (1997) -- GHRP-6 and Hexarelin Reference Data [9]:

In human volunteers receiving GHRP-6 and hexarelin at GH-effective doses:

• GHRP-6 at 1 μg/kg IV produced significant increases in ACTH, cortisol, and prolactin alongside GH release
• Hexarelin at 1 μg/kg IV produced approximately 40% cortisol increase and approximately 80% prolactin increase at the standard GH-releasing dose
• These off-target endocrine effects are dose-dependent and clinically relevant for repeated-dose protocols

Clinical Implications of Hormonal Selectivity:

The absence of cortisol and ACTH stimulation means ipamorelin does not activate the hypothalamic-pituitary-adrenal (HPA) axis, avoiding the catabolic and metabolic consequences of repeated cortisol elevation (muscle wasting, fat redistribution, insulin resistance, bone loss, immune suppression). The absence of prolactin stimulation avoids potential effects on reproductive function and galactorrhea. These properties make ipamorelin the most hormonal-axis-sparing GH secretagogue characterized in published research [1][10][11].

Observed Adverse Effects in Clinical Studies

Beck et al. (2014) -- Phase II Trial (n=114) [5]:

In the randomized, double-blind, placebo-controlled trial of ipamorelin (0.03 mg/kg IV every 8 hours for up to 7 days) in bowel resection patients:

• Nausea: Reported in both groups; incidence similar between ipamorelin and placebo
• Headache: Mild, transient; comparable rates in both groups
• Diarrhea: Observed in a minority of patients; rates did not differ significantly between groups
• Abdominal distension: Expected in the post-surgical setting; comparable incidence
• Serious adverse events: No SAEs were attributed to ipamorelin
• Overall tolerability: Adverse event rates were comparable between ipamorelin and placebo groups, indicating that ipamorelin was well tolerated over repeated dosing for up to 7 days

Gobburu et al. (1999) -- Pharmacokinetic Study [2]:

In healthy male volunteers receiving single IV doses of ipamorelin:

• No clinically significant adverse events were reported
• Vital signs, ECG, and laboratory parameters remained within normal limits
• No injection site reactions noted with IV administration

Appetite Effects

Unlike GHRP-6, which produces strong appetite stimulation through hypothalamic NPY/AgRP activation within 20-30 minutes of injection, ipamorelin produces minimal orexigenic effects at GH-releasing doses [1][10]. This suggests a more selective GHS-R1a interaction that preferentially engages the pituitary somatotroph signaling pathway over hypothalamic appetite-regulating circuits. The reduced appetite stimulation is clinically relevant for patients in whom hunger and weight gain are undesirable.

Theoretical Concerns

As with any agent that stimulates the GH-IGF-1 axis, theoretical long-term risks include:

• Insulin resistance and impaired glucose tolerance
• Fluid retention
• Joint pain and carpal tunnel syndrome
• Potential influence on neoplastic cell growth

None of these effects have been specifically documented for ipamorelin in published clinical studies, and no long-term safety data exist [5][6].

Tachyphylaxis

Preclinical data suggest that repeated administration of GH secretagogues can lead to attenuation of the GH response over time [4]. Hexarelin, the most potent GHRP, demonstrates pronounced desensitization with continued use, with significant decline in GH response by week 4 of daily administration and further attenuation by week 16 [12]. Whether ipamorelin exhibits a similar pattern at clinically relevant dosing intervals has not been adequately studied in humans, though its selectivity and different receptor interaction profile suggest it may be less prone to tachyphylaxis than hexarelin [10][11].

Comparative Effectiveness: Ipamorelin vs Other GH Secretagogues

The following comparison is based on published preclinical and clinical data from studies of each compound. Direct head-to-head trials between these agents are limited; most comparisons are derived from cross-study analysis.

Comprehensive Comparison Table

| Parameter | Ipamorelin | GHRP-6 | GHRP-2 | Hexarelin | MK-677 (Ibutamoren) | |---|---|---|---|---|---| | Structure | Pentapeptide [1] | Hexapeptide | Hexapeptide | Hexapeptide | Non-peptide spiropiperidine | | Molecular Weight | 711.85 Da | 873.01 Da | 817.97 Da | 887.04 Da | 528.66 Da (free base) | | Route | SC, IV [1][2] | SC, IV, IN, oral | SC, IV | SC, IV, IN, oral | Oral only [16] | | Half-life | ~2 hours [2] | ~2.5 hours (elim.) | ~25-30 min (IV) | ~70 min (IV) | ~24 hours [16] | | GH Potency | Moderate-High [1] | High | High | Highest [15] | High (sustained) [16] | | GH Peak Timing | 30-60 min [2] | 15-30 min | 15-30 min | 15-30 min | 1-2 hours [16] | | GH Duration | 2-3 hours [2] | 60-90 min | 60-90 min | 60-90 min | Sustained 24h [16] | | Cortisol | None at any dose [1] | Dose-dependent elevation [9] | Moderate elevation | ~40% increase at 0.5 μg/kg [15] | Transient/variable [6][14] | | ACTH | None at any dose [1] | Dose-dependent elevation [9] | Moderate elevation | Significant elevation [15] | Variable [14] | | Prolactin | None at any dose [1] | Dose-dependent elevation [9] | Moderate elevation | ~80% increase [15] | ~23% increase [16] | | Appetite Stimulation | Minimal [1] | Strong [10] | Moderate | Moderate | Moderate-Strong [16] | | Desensitization | Not well studied; expected mild [11] | Moderate [10] | Moderate | Pronounced (significant by week 4) [12] | Minimal over 2 years [14] | | FDA Status | Not approved | Not approved | Not approved | Not approved | Not approved |

Ipamorelin vs GHRP-6

GHRP-6 was the first GHRP characterized (Bowers et al. 1984) and ipamorelin was specifically designed to improve upon its selectivity profile [1]. Both compounds produce comparable maximal GH release at their respective effective doses. The critical differences are:

• Cortisol/ACTH: GHRP-6 elevates cortisol and ACTH in a dose-dependent manner at or near GH-effective doses; ipamorelin produces no cortisol or ACTH elevation at any dose tested [1][9]
• Prolactin: GHRP-6 elevates prolactin at GH-effective doses; ipamorelin does not [1]
• Appetite: GHRP-6 produces the strongest appetite stimulation among all GHRPs through hypothalamic NPY/AgRP activation, occurring within 20-30 minutes of injection; ipamorelin produces minimal appetite effects [10]
• Clinical applications: GHRP-6 has been more extensively studied in humans, particularly as a GH deficiency diagnostic tool (GHRH+GHRP-6 test) and for cytoprotective effects. Ipamorelin's clinical data are limited to PK studies and the Phase II POI trial [5]

Ipamorelin vs GHRP-2

GHRP-2 is considered the most potent hexapeptide GHRP per unit dose for GH release and has been used clinically in Japan as a diagnostic GH stimulation test. Compared to ipamorelin:

• GH potency: GHRP-2 may produce slightly higher peak GH levels per unit dose
• Selectivity: GHRP-2 is more selective than GHRP-6 but less selective than ipamorelin. It produces moderate cortisol, ACTH, and prolactin elevation at GH-effective doses [4][10]
• Appetite: GHRP-2 produces less appetite stimulation than GHRP-6 but more than ipamorelin

Ipamorelin vs Hexarelin

Hexarelin produces the highest acute GH release of any GHRP but at the cost of the broadest off-target hormonal activation and the most pronounced tachyphylaxis:

• GH potency: Hexarelin produces higher peak GH than ipamorelin at equivalent doses [15]
• Cortisol/ACTH: Hexarelin produces approximately 40% cortisol increase and significant ACTH elevation at its standard GH-releasing dose of 0.5-1.0 μg/kg IV; ipamorelin produces none [1][15]
• Prolactin: Hexarelin increases prolactin approximately 80% from baseline; ipamorelin does not [15]
• Desensitization: Hexarelin demonstrates pronounced GH response attenuation within 4 weeks of daily use, with further decline by week 16 [12]. Ipamorelin's desensitization profile is less well characterized but is expected to be milder based on its selectivity [11]
• Cardiac effects: Hexarelin has demonstrated direct, GH-independent cardioprotective effects through CD36 receptor binding in cardiomyocytes. Ipamorelin does not appear to share this property

Ipamorelin vs MK-677 (Ibutamoren)

MK-677 and ipamorelin are fundamentally different in administration route and pharmacokinetic profile, though both act on GHS-R1a:

• Administration: MK-677 is oral (once daily); ipamorelin requires SC or IV injection [16]
• Half-life: MK-677 has a 24-hour half-life producing sustained GH/IGF-1 elevation; ipamorelin's 2-hour half-life produces discrete GH pulses [2][16]
• Selectivity: Ipamorelin is more hormonally selective. MK-677 produces transient cortisol increases (47 nmol/L increase over 2 years in one trial), prolactin elevation (~23%), and significant appetite stimulation [14][16]
• Desensitization: MK-677 has been administered daily for up to 2 years without significant loss of IGF-1-elevating effect [14]. Ipamorelin's long-term desensitization profile is less characterized
• Clinical data: MK-677 has far more extensive clinical trial data (multiple Phase II trials across aging, obesity, osteoporosis, GH deficiency, hip fracture). Ipamorelin has limited human data [5][14]
• Safety signals: MK-677 has documented concerns regarding insulin resistance and a higher rate of congestive heart failure in elderly hip fracture patients. Ipamorelin has not generated comparable safety signals, though its human exposure database is much smaller [5][14]

CJC-1295 + Ipamorelin Combination Rationale

The combination of CJC-1295 (a GHRH analog acting on the GHRH receptor) with ipamorelin (a GHS-R1a agonist) is frequently discussed in the context of GH optimization. The pharmacological rationale rests on the synergistic interaction between the two signaling pathways:

• GHRH receptor pathway (CJC-1295): Activates cAMP/protein kinase A signaling in somatotrophs, increasing GH gene transcription and GH synthesis
• GHS-R1a pathway (ipamorelin): Activates phospholipase C/IP3/calcium signaling, directly triggering GH vesicle exocytosis

When both pathways are activated simultaneously, the combined GH response substantially exceeds the arithmetic sum of the individual responses, a phenomenon extensively documented for the GHRH+GHRP combination [13]. This synergy has been most rigorously demonstrated with GHRH+GHRP-6 in human studies, where combined administration produced GH peaks far exceeding either agent alone. The same pharmacological principle applies to CJC-1295+ipamorelin, though direct clinical trial data for this specific combination have not been published.

The combination is theoretically attractive because:

1. CJC-1295 without DAC (Mod GRF 1-29) has a short half-life (~30 minutes), providing a GHRH signal that aligns temporally with ipamorelin's GH pulse
2. CJC-1295 with DAC has an extended half-life of 6-8 days, providing a sustained GHRH "background" signal upon which ipamorelin pulses can act [13]
3. Ipamorelin contributes the selectivity advantage -- no cortisol, ACTH, or prolactin spillover -- which would also apply in the combination context
4. Neither CJC-1295 nor ipamorelin individually produce the cortisol or prolactin elevation seen with less selective secretagogue combinations

No controlled clinical trials have evaluated the CJC-1295 + ipamorelin combination for any endpoint.

Researched Applications

All applications listed below are investigational. Ipamorelin is not approved for clinical use.

Growth Hormone Stimulation

The primary pharmacological effect of ipamorelin is the stimulation of endogenous GH release. In human volunteers, intravenous administration of 1 μg/kg produced GH peaks within 30-60 minutes, with levels returning to baseline within 2-3 hours [2]. The GH response was dose-dependent and reproducible across multiple administrations [2].

Post-Surgical Gastrointestinal Recovery

The most advanced clinical application studied for ipamorelin was the management of postoperative ileus (POI), a common complication following abdominal surgery. Ghrelin receptor agonism has prokinetic effects on the gastrointestinal tract, and ipamorelin was investigated for its potential to accelerate recovery of bowel function [5].

Beck et al. (2014) conducted a Phase II, randomized, double-blind, placebo-controlled trial in 114 patients undergoing bowel resection. Patients received ipamorelin (0.03 mg/kg IV) or placebo every 8 hours for up to 7 days. The study reported a trend toward earlier time to first bowel movement and tolerance of solid food in the ipamorelin group, though the primary composite endpoint did not reach statistical significance [5].

Bone Density

In a preclinical study, Andersen et al. (2001) demonstrated that ipamorelin partially counteracted the bone-formation suppression induced by glucocorticoid treatment in adult rats. Animals receiving ipamorelin showed increased bone formation rates and osteocalcin levels compared to glucocorticoid-only controls [7]. These findings have not been replicated in human studies.

Body Composition

No controlled clinical trials have directly evaluated the effects of ipamorelin on body composition (lean mass, fat mass) in humans. Theoretical effects on body composition are inferred from the known actions of GH on protein synthesis and lipolysis, but direct evidence is lacking for this specific compound.

Clinical Evidence Summary

The clinical evidence base for ipamorelin is limited:

• Gobburu et al. (1999): Pharmacokinetic-pharmacodynamic modeling in healthy volunteers established the dose-response relationship for GH release following IV ipamorelin. The study confirmed rapid absorption, a terminal half-life of approximately 2 hours, and dose-proportional GH stimulation [2].

• Beck et al. (2014): Phase II trial of ipamorelin for postoperative ileus in 114 bowel resection patients. Ipamorelin was well tolerated. The primary composite endpoint (time to tolerate solid food and first bowel movement and first flatus) did not reach significance versus placebo, though individual components showed numerical trends favoring ipamorelin [5].

• Raun et al. (1998): Primarily an animal study, this paper established the selectivity profile of ipamorelin and included limited human pharmacological data confirming GH release without cortisol or prolactin elevation [1].

No Phase III efficacy trials have been completed for any indication.

Dosing in Published Research

The following doses have been used in clinical research settings. This information is provided for educational reference only and does not constitute medical advice or a recommendation for use.

| Protocol | Dose | Frequency | Route | Source | |---|---|---|---|---| | GH stimulation testing | 1 μg/kg | Single dose | Intravenous | Raun et al. 1998 [1]; Gobburu et al. 1999 [2] | | Postoperative ileus | 0.03 mg/kg | Every 8 hours (up to 7 days) | Intravenous | Beck et al. 2014 [5] |

Dose-ranging studies in humans beyond the above protocols have not been published in peer-reviewed literature.

Key dosing observations from the literature:

• The GH dose-response curve reaches a plateau at approximately 0.1 mg/kg in animal models, consistent with receptor saturation kinetics [1][2]
• At the standard clinical research dose of 1 μg/kg IV, GH peak occurs at 30-60 minutes and returns to baseline within 2-3 hours [2]
• Unlike GHRP-6, increasing ipamorelin dose above the GH saturation point does not produce cortisol, ACTH, or prolactin release, providing a wider therapeutic window [1]
• Repeated dosing at 0.03 mg/kg IV every 8 hours for up to 7 days was well tolerated without evidence of acute tachyphylaxis [5]

Regulatory Status

FDA: Ipamorelin is not approved by the U.S. Food and Drug Administration for any indication. It was investigated in clinical trials sponsored by Helsinn Therapeutics (for postoperative ileus) but has not advanced to Phase III [5].

WADA: Ipamorelin is prohibited by the World Anti-Doping Agency under category S2 (Peptide Hormones, Growth Factors, Related Substances, and Mimetics) at all times, both in-competition and out-of-competition [8].

U.S. Compounding Update (February 2026): On February 27, 2026, HHS Secretary Robert F. Kennedy Jr. announced that ipamorelin would be among approximately 14 peptides moved from FDA Category 2 (effectively banned from compounding) back to Category 1, restoring legal access through licensed compounding pharmacies with a physician's prescription. This reclassification does not constitute FDA approval. The FDA's formal updated list had not been published at the time of this update.

Legal Status: Ipamorelin is available through unregulated channels marketed for "research use only." Products obtained outside of regulated pharmaceutical manufacturing carry risks of contamination, mislabeling, and inconsistent potency.

Related Peptides

See also: CJC-1295, GHRP-6, Hexarelin, MK-677

• CJC-1295 — A GHRH analog that acts through the GHRH receptor rather than the ghrelin receptor. Frequently discussed alongside ipamorelin due to the complementary nature of GHRH and GHS-R1a signaling pathways in GH release. The combination exploits the synergy between cAMP-dependent (GHRH-R) and calcium-dependent (GHS-R1a) pathways.

• GHRP-6 — The founding GHRP from which ipamorelin was derived through structure-activity optimization. Comparable GH potency but with dose-dependent cortisol, ACTH, prolactin elevation and strong appetite stimulation -- the exact properties ipamorelin was designed to eliminate.

• Hexarelin — The most potent GHRP in terms of acute GH release but with the broadest off-target hormonal effects and the most pronounced receptor desensitization. Unique among GHRPs for GH-independent cardioprotective effects via the CD36 receptor.

• MK-677 — A non-peptide, orally active GHS-R1a agonist with a 24-hour half-life enabling once-daily oral dosing and sustained IGF-1 elevation. More extensive clinical data but less hormonal selectivity than ipamorelin.

References

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