Ipamorelin
The most selective growth hormone secretagogue (GHS) available, stimulating GH release from the pituitary with minimal effects on cortisol, prolactin, or appetite. Considered the mildest and safest GHRP, making it the most widely prescribed growth hormone peptide in anti-aging and regenerative medicine. Often the recommended starting point for patients new to GH-optimizing peptide therapy.
Typical Dosage
Standard: 200-300 mcg subcutaneous two or three times daily. Often combined with CJC-1295 (no DAC) 100-300 mcg in the same syringe for synergistic GH release. Typically dosed before bed and/or upon waking on an empty stomach.
Administration
Subcutaneous injection
Mechanism of Action
Ipamorelin is a pentapeptide growth hormone secretagogue that binds selectively to the growth hormone secretagogue receptor type 1a (GHS-R1a), the same receptor that endogenous ghrelin activates. However, unlike ghrelin and other GHRPs such as GHRP-6 and Hexarelin, ipamorelin demonstrates remarkable selectivity — it stimulates robust GH release while causing minimal elevation of cortisol, prolactin, and ACTH at therapeutic doses.
At the molecular level, ipamorelin binding to GHS-R1a on pituitary somatotrophs activates a Gq/11-coupled signaling cascade that stimulates phospholipase C (PLC), generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 triggers calcium release from intracellular stores, while DAG activates protein kinase C. The resulting rise in intracellular calcium triggers GH vesicle exocytosis. This mechanism is distinct from and synergistic with the cAMP pathway activated by GHRH, which is why combining ipamorelin with a GHRH analogue like CJC-1295 produces amplified GH pulses.
The selectivity of ipamorelin is attributed to its specific binding conformation at the GHS-R1a receptor, which activates the GH release pathway without engaging the broader hypothalamic-pituitary-adrenal axis. It does not significantly activate appetite centers in the hypothalamus at standard doses, nor does it stimulate ACTH release from corticotrophs. This clean side-effect profile has made it the most widely prescribed growth hormone secretagogue in anti-aging and regenerative medicine, often considered the safest starting point for patients new to GH-optimizing peptide therapy.
Regulatory Status
Not FDA approved. One of the most commonly prescribed peptides in anti-aging medicine. Available through compounding pharmacies.
Risks & Safety
Common: headache, lightheadedness, transient water retention, injection site irritation. Serious: theoretical risk of promoting existing tumor growth via GH/IGF-1 elevation (class effect for all GH secretagogues). Rare: allergic reactions, vasovagal response. One of the best-tolerated GH peptides with the cleanest side-effect profile among GHRPs. Not FDA approved.
Research Papers
2Published: December 31, 2025
Abstract
Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care.
Published: December 31, 2025
Abstract
Therapeutic peptides are short-chain amino acids that regulate cellular functions and facilitate biochemical processes. In recent years, there has been significant growth in the global market for therapeutic peptides and thus its popularity among patients. Given the increase in the development of peptides and increased marketing to patients for orthopaedic injuries, it is critical for orthopaedic surgeons to understand the current evidence behind these therapeutic peptides.
Related Peptides
ACE-031
A soluble activin receptor type IIB fusion protein (ActRIIB-Fc) that acts as a broad-spectrum myostatin/activin 'decoy receptor,' intercepting these muscle-growth inhibitors before they reach target tissues. Produced rapid muscle mass gains in clinical trials without exercise, but development was halted due to vascular side effects caused by inadvertent blockade of BMP-9/BMP-10 endothelial signaling.
AEDG Peptide
A tetrapeptide (Ala-Glu-Asp-Gly) identical to Epithalon's core active sequence — effectively the same compound. Studied for telomerase activation and pineal gland regulation, promoting melatonin production and potentially slowing cellular aging through telomere maintenance. Part of the Khavinson bioregulator peptide family developed at the Institute of Bioregulation and Gerontology in St. Petersburg.
AICAR
5-Aminoimidazole-4-carboxamide ribonucleotide — an endogenous intermediate of purine biosynthesis that activates AMP-kinase (AMPK), the cellular energy sensor triggered by exercise. Mimics the metabolic effects of endurance exercise at the cellular level, enhancing fat oxidation, glucose uptake, and mitochondrial biogenesis. Banned by WADA as a metabolic modulator after detection in professional cycling.
BPC-157
Body Protection Compound-157 — a synthetic pentadecapeptide (15 amino acids) derived from a protective protein found in human gastric juice. The most widely studied regenerative peptide, with extensive animal research demonstrating healing effects on tendons, ligaments, muscles, the gut, and multiple organ systems. Uniquely stable in gastric acid, enabling both injectable and oral administration.