Ipamorelin

Technical data

INN name

Ipamorelin

Development code

NNC 26-0161

CAS

170851-70-4

Molecular formula

C38H49N9O5

Molecular weight

711.85 g/mol

Identity and composition

Ipamorelin is a synthetic pentapeptide of sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (with the non-canonical amino acids D-2-Nal and D-Phe), molecular mass 711.86 Da. It is a selective agonist of the growth hormone secretagogue receptor (GHSR-1a), also known as the ghrelin receptor.

It was developed by the Danish company Novo Nordisk in the late 1990s within its GH secretagogue program (NN703). Its design sought superior selectivity compared to other GHRPs of the time (GHRP-2, GHRP-6, Hexarelin), minimizing cross-effects on cortisol, prolactin, and aldosterone.

Structure and properties: a linear pentapeptide with C-terminal amidation, high aqueous solubility, good physicochemical stability and high subcutaneous bioavailability.

Key differentiating feature: SELECTIVITY: induce liberación selectiva de GH sin elevar cortisol, prolactina, ACTH ni aldosterona a dosis terapéuticas (a diferencia de GHRP-2, GHRP-6, Hexarelina), lo que la convierte en el cleaner GHRP for research.

Mixed peripheral-central mechanism: direct action on pituitary somatotrophs (releases stored GH) and central action on the hypothalamic arcuate nucleus (inhibits somatostatin, "releasing the brake"). This dual action underpins the synergy with GHRH analogs.

Se utiliza como research molecule en estudios del eje somatotropo, motilidad gastrointestinal, gastroparesia y, particularmente, en combinaciones con GHRH análogos. Novo Nordisk completó fase II en gastroparesia post-operatoria pero suspendió el desarrollo en 2010.

Mechanism of action

Ipamorelin is agonist of the GHSR-1a receptor (Growth Hormone Secretagogue Receptor 1a), also known as the ghrelin receptor. Its mechanism is complementary to that of GHRH analogs.

Molecular cascade:

1. Unión al receptor GHSR-1a acoplado a proteína Gq/11 (no Gs como GHRH).
2. Activación de fosfolipasa C → IP3 + DAG.
3. Movilización de calcio intracelular y activación de PKC.
4. Despolarización de somatotropas → liberación de GH.
5. Simultaneous central action on the arcuate nucleus: inhibition of somatostatinergic neurons and of the inhibitory tone on somatotrophs.
6. Plasma GH pulse (5–15× over baseline), peak at 15–30 min → IGF-1.

Induced release pattern: a single well-defined pulse, duration 2–3 hours, magnitude comparable to or greater than GHRP-2 with much cleaner side effects.

Selectividad (característica diferencial CLAVE): no estimula cortisol (vs GHRP-6, which raises it 2-3×), prolactin (vs GHRP-2/6, which can double it), ACTH (vs Hexarelin), or aldosterone, and no effects on appetite (vs GHRP-6, orexigénico marcado).

Sinergia con GHRH análogos: the GHRH analog activates GHRHR (Gs → cAMP → PKA) and Ipamorelin activates GHSR-1a (Gq/11 → calcium + PKC) plus the arcuate nucleus (inhibits somatostatin). Non-overlapping mechanisms + removal of the endogenous brake → release synergistic (no aditiva); el pulso combinado puede alcanzar 5–10× la suma de pulsos individuales.

Direct GI effects: accelerated gastric motility (ghrelinergic mechanism), the basis of the phase II program in post-surgical gastroparesis.

Preservation of the endogenous axis: stimulates endogenous production without replacing GH; the short half-life avoids feedback suppression.

Pharmacokinetics

Absorption:

• Subcutaneous: biodisponibilidad alta (>70% estimado).
• Tmax: 15–30 minutes.

Distribution: broad after parenteral administration; moderate crossing of the blood-brain barrier (necessary for the action on the arcuate nucleus).

Plasma half-life: approximately 2 hours, mayor que GHRP-6 (~15 min) y que CJC-1295 Sin DAC (~30 min).

Metabolism: proteolytic degradation by serum and tissue peptidases. Elimination: predominantly renal.

Duration of the biological effect:

• Induced GH pulse: ~2–3 hours.
• Secondary elevation of IGF-1 (with chronic dosing): 24–48 hours.
• No plasma accumulation with 1-3×/day dosing.

Dosing frequency: 1–3 times/day allows separate physiological pulses; the intermediate half-life gives greater flexibility than GHRP-6 (shorter) or CJC-1295 DAC (much longer).

Serum stability: degradation in 2–4 hours in vitro in human serum; no significant effect of food on absorption.

Combinación con CJC-1295 Sin DAC: simultaneous subcutaneous co-administration, GH peak at 15–30 min; half-lives that leave both peptides active at the receptor at the same time, maximizing synergy.

PK linearity: approximately linear in the documented 50–500 µg range.

Scientific evidence

The evidence on Ipamorelin comes from extensive preclinical studies y phase I/II clinical trials by Novo Nordisk before the program was discontinued in 2010.

Foundational preclinical studies:

• Raun et al. (Eur J Endocrinol 1998): original characterization; demonstrated GH selectivity without significant effects on cortisol, prolactin, ACTH, or aldosterone in rat, pig, and monkey.
• Head-to-head comparisons vs GHRP-6 and Hexarelin showing a cleaner profile.

Pharmacokinetics en humanos: caracterización de pulsos GH, vida media y patrones de respuesta; confirmación de selectividad somatotropa.

Fase II en gastroparesia post-operatoria (Novo Nordisk): estudios en pacientes post-cirugía abdominal con íleo prolongado; aceleración significativa de motilidad gástrica. Programa suspendido hacia 2010 por razones estratégicas, no de seguridad.

Combinación con GHRH análogos: GHRH + GHRP synergy extensively documented; Ipamorelin + CJC-1295 without DAC is the most documented in non-industry literature.

Animal models: increase in lean mass with chronic dosing, improved tissue healing (IGF-1) and studies of somatotropic aging in rodents.

Cardiovascular preclínica: efectos cardioprotectores en isquemia-reperfusión y mejora de función ventricular en insuficiencia cardíaca (receptor ghrelinérgico cardíaco).

Limitations: the discontinuation left the clinical evidence truncated at phase II; the phase III trials were never conducted and current use is mostly as a research reagent.

Research applications

Applications documented in research:

Somatotropic axis (main line):

• Respuesta GH a estimulación ghrelinérgica selectiva.
• Deficiencia parcial GH del adulto; envejecimiento somatotropo (somatopausa).

Gastrointestinal (línea Novo Nordisk): gastroparesia post-operatoria (fase II), íleo paralítico.

Body composition: increase in lean mass (with GHRH analogs), reduction of visceral fat, muscle preservation under caloric restriction.

Recovery and regeneration: cicatrización tisular (IGF-1), reparación muscular post-ejercicio, tendinopatía crónica.

Cardiovascular preclínica: cardioprotección en isquemia-reperfusión y mejora de función ventricular (receptor ghrelinérgico cardíaco).

Sleep: mejora de sueño profundo (pulsos GH nocturnos). Caquexia y sarcopenia: research in aging and chronic disease.

Standard combined applications:

• Ipamorelin + CJC-1295 No DAC: the most documented for synergy and selectivity. Typical doses 100–200 µg + 100 µg subcutaneous, 1–3 times/day.
• Ipamorelin + Tesamorelin: mismo concepto. + Sermorelin: menor potencia individual.

Vías: subcutaneous (standard), intramuscular (acceptable); oral not viable (GI degradation). All application remains strictly investigational; no use has been approved for human therapeutics.

Research protocols

Los protocolos en literatura preclínica siguen un esquema basado en physiological pulses.

Typical doses (research):

• 100–300 µg per subcutaneous dose (widely studied range); most common standard dose 200 µg; frequency 1–3 times/day.

Most documented regimen: 200 µg × 3 times/day:

• Morning fasted, mid-afternoon before training (sports research), and at night before sleep.

Simplified schedule: 300 µg × once/day at night: maximiza el pulso GH durante el sueño.

Combinaciones recomendadas:

• Ipamorelin 200 µg + CJC-1295 DAC-free 100 µg: reference combination, well-documented synergy.
• Ipamorelina 200 µg + Tesamorelina (~1-2 mg): alternativa con GHRH aprobado FDA.

NON-recommended combinations:

• Ipamorelin + CJC-1295 DAC: the sustained GHRH elevation saturates the system; minimal synergy.
• Ipamorelina + GHRP-2/6: ambos GHRP, redundantes y suman efectos colaterales.

Duration: short 8–12 weeks; extended 12–24 weeks with 2–4 week breaks to avoid desensitization of the GHSR. Typical cycling: 12 weeks on / 4 weeks off.

Timing: administer fasted or ≥1.5 h after a meal; wait 20–30 min before eating so that the GH pulse occurs without interference. The combination benefits from fasting.

Animal models: rata 10–50 µg/kg/dosis; ratón 20–100 µg/kg/dosis.

Monitoring: IGF-1 basal y a 4–8 semanas, glucemia, función tiroidea y composición corporal por DXA en estudios prolongados.

Reconstitution

Lyophilized ipamorelin is reconstituted with bacteriostatic water (BAC) preferably.

Standard procedure:

1. Equilibrate vial and solvent to room temperature for 15 min.
2. Clean the stopper with 70% isopropanol.
3. Inject BAC slowly onto the side wall of the vial.
4. Do not shake: swirl gently to dissolve in 1–2 min.
5. Solución debe ser clear and colorless.

Reference concentrations:

2 mg vial:

• 1 mL BAC → 2,000 µg/mL (200 µg = 0.1 mL = 10 IU in a U-100 syringe)
• 2 mL BAC → 1,000 µg/mL (200 µg = 0.2 mL = 20 IU)

5 mg vial:

• 1 mL BAC → 5,000 µg/mL (200 µg = 0.04 mL = 4 IU)
• 2.5 mL BAC → 2,000 µg/mL (200 µg = 0.1 mL = 10 IU)
• 5 mL BAC → 1,000 µg/mL (200 µg = 0.2 mL = 20 IU)

Syringe: insulina U-100 de 0.3–0.5 mL, aguja 30–32G × 6–8 mm. Route: subcutánea estricta (abdomen, muslo, deltoides), rotando sitios. Dose calculation: volume (mL) = dose (µg) / concentration (µg/mL).

Compatibility with CJC-1295 No DAC: they can be mixed in the same syringe just before injecting without any documented loss of activity; premixes for prolonged storage are less well characterized. With CJC-1295 DAC the combination is not recommended.

Stability and storage

Sealed lyophilized vial:

• Storage at 2–8 °C, protected from light; stability up to 24 months according to the manufacturer.
• Transient tolerance to room temperature: up to 30 days.

Vial reconstituted with BAC:

• Strict storage at 2–8 °C; stability 28 days (more stable than the CJC-1295 analogs because of its simple pentapeptide structure). Do not freeze; protect from light.

Reconstituido con agua estéril sin conservador: uso inmediato o dentro de 24 h refrigerado.

Thermal sensitivity: tolerates up to 25 °C transiently; better thermal stability than the GHRH analogs because of lower structural complexity.

Chemical sensitivity: pH óptimo 5–7, estable en rango 4–8; sin reactividad especial (sin grupos maleimida ni cisteínas libres).

Degradation indicators: turbidez, partículas, cambio de color o precipitado → descartar.

Frozen aliquots: posibles a -20 °C en viales individuales; una sola congelación-descongelación (extiende vida útil hasta ~90 días).

Premezclas con CJC-1295 Sin DAC: limited studies suggest stability of 14–21 days refrigerated, though it is preferable to keep them separate.

Safety profile

Ipamorelin presents one of the more favorable safety profiles among the GHRPs because of its superior selectivity.

Common adverse events (mild, transient):

• Sensación de calor u "hormigueo" post-dosis: 10–20%.
• Mild headache: 5–10%.
• Injection site reactions: 2–5% (eritema).
• Somnolencia (con dosis nocturnas).
• Mild transient dizziness: 5%.

What it does NOT significantly cause (vs other GHRPs):

• Does NOT raise cortisol (a diferencia de GHRP-6).
• Does NOT raise prolactin (a diferencia de GHRP-2/6).
• Does NOT raise ACTH (a diferencia de Hexarelina) ni aldosterona.
• Does NOT stimulate appetite markedly (unlike the orexigenic GHRP-6).

This selectivity is the main argument for preferring Ipamorelin over other GHRPs in research.

Events associated with the GH/IGF-1 response: retención hídrica leve ocasional con dosificación crónica; parestesias en manos poco comunes con dosis bajas/medias; artralgias ocasionales; hiperglucemia leve (vigilancia en diabéticos).

Infrequent events: alteración del eje tiroideo (ocasional en uso >12 semanas) y cambios en sensibilidad insulínica (monitoreo en uso prolongado).

Theoretical concerns with prolonged use:

• Consecuencias no caracterizadas de la estimulación crónica del eje somatotropo.
• Oncological risk: GH/IGF-1 are mitogenic; caution in preexisting neoplasia.
• Desensibilización del GHSR-1a con uso muy prolongado (ciclar).

Absolute contraindications: neoplasia activa o historia oncológica reciente, diabetes mal controlada, retinopatía proliferativa, embarazo, lactancia, menores.

Relative contraindications: túnel carpiano preexistente, trastornos tiroideos no controlados, insuficiencia hepática/renal moderada–severa.

Interactions: glucocorticoides (reducen respuesta GH), insulina (ajuste por efecto contrarregulador), otros GHRP (redundancia sin ganancia).

WADA status: prohibida en deportes competitivos desde 2013, categoría S2. HPLC purity: idealmente >99%.

Comparative context

vs GHRP-2 (Pralmorelin): more potent individually (GH pulse ~15-20× vs ~5-15× for Ipamorelin), but raises prolactin and cortisol significantly; Ipamorelin is preferred for its superior selectivity.

vs GHRP-6: markedly orexigenic and raises cortisol more; Ipamorelin is preferred when an orexigenic effect is not sought.

vs Hexarelin: very potent but with more side effects (cortisol, ACTH) and faster desensitization; Ipamorelin is preferred for chronic use.

vs Ghrelin (endogenous peptide): natural ligand of GHSR-1a, very short half-life (~30 min); Ipamorelin is the practical synthetic analog.

vs CJC-1295 No DAC (different class): GHRH analog (GHRHR receptor) vs GHRP (GHSR-1a); mechanisms complementarios, frecuentemente combinados por sinergia, no alternativas.

vs IGF-1 LR3: acts directly on IGF-1 receptors (greater mitogenic potency and risk); Ipamorelin acts upstream. vs MGF: variante de IGF-1, mecanismo distinto.

Practical recommendation: Ipamorelina es el GHRP de elección moderna por su selectividad; combinada con CJC-1295 Sin DAC representa el estándar de referencia en estimulación sinérgica del eje somatotropo.

History and development

Ipamorelin was developed by Novo Nordisk (Denmark) in the late 1990s within its growth hormone secretagogue program (internal project NN703), seeking a GHRP with selectivity superior to GHRP-2, GHRP-6, and Hexarelin.

Chronological milestones:

• 1994–1996: desarrollo y caracterización preclínica inicial.
• 1998: publicación seminal de Raun et al. (Eur J Endocrinol) caracterizando el perfil único de selectividad.
• 1998–2010: fase I y II en gastroparesia post-operatoria e íleo post-quirúrgico, con estudios farmacocinéticos extendidos.
• 2010: Novo Nordisk suspende el desarrollo clínico por razones estratégicas (no de seguridad).
• 2013: WADA incluye Ipamorelina en la lista prohibida (categoría S2).

Razones de suspensión (2010): reestructuración del pipeline hacia diabetes (insulinas, GLP-1) y obesidad; mercado de gastroparesia limitado vs costos de fase III; sin problemas de seguridad reportados.

Origin of the name: "Ipam" (Novo Nordisk internal coding) + "orelin" (suffix of GHRP/ghrelin analogs). Other morelins: Macimorelin (FDA-approved in 2017 for the diagnosis of adult GH deficiency), Anamorelin (cancer cachexia), and Capromorelin (veterinary).

Regulatory context: no cuenta con aprobación de ninguna autoridad (FDA, EMA, COFEPRIS) for human use; Macimorelin does have FDA diagnostic approval. WADA has banned it since 2013. Novo Nordisk's patents expired, allowing generic production as a research reagent.

FAQ

Customer reviews

Average rating: 4.9 out of 5, based on 16 customer ratings.

Certificate of analysis per batch

Ipamorelin batches with certificate of analysis published in the COA catalog:

• Lot EXO010626145A — 2 mg, issued 2026-05-30
• Lot EXO010626145C — 5 mg, issued 2026-05-30

Scientific references (3)

Peer-reviewed literature on Ipamorelin, with its PubMed identifier where available:

• Ipamorelin for postoperative ileus – Phase 2 study (Beck DE, Sweeney WB, McCarter MD, et al. · International Journal of Colorectal Disease · 2014) — Randomized phase 2 trial evaluating ipamorelin in the recovery of postoperative ileus after major abdominal surgery. PMID 25331030.
• Ipamorelin: The first selective growth hormone secretagogue (Raun K, et al. · European Journal of Endocrinology · 1998) — First study characterizing Ipamorelin as a selective GH secretagogue. PMID 9849822.
• A new series of highly potent growth hormone-releasing peptides derived from ipamorelin (Ankersen, et al. · Journal of Medicinal Chemistry · 1998) PMID 9733495.

Guides and articles about Ipamorelin

Lecturas del blog de EXOMA que la editorial asoció a este compuesto:

• Ipamorelin in Mexico: GHRP pentapeptide selective for the ghrelin receptor
• CJC-1295 + Ipamorelin: Stack Mechanism in Research
• Tesamorelin: Growth Hormone-Releasing Agent with Clinical Evidence

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• CJC-1295 (DAC)
• CJC-1295 (Without DAC)