Ipamorelin

Ipamorelin is a synthetic peptide that acts as a growth hormone secretagogue, stimulating the release of growth hormone from the pituitary gland. It is composed of five amino acids and is structurally designed to selectively bind to the ghrelin receptor.

Ipamorelin is believed to promote muscle growth and fat metabolism by increasing growth hormone levels. It may also support recovery, tissue repair, and overall energy regulation. These effects are linked to its ability to enhance anabolic processes in the body.

The peptide Ipamorelin has been shown in animal studies to selectively stimulate growth hormone release without significantly affecting other hormones such as ACTH or cortisol, thereby supporting lean‑body‑mass growth and bone formation. For example, in rats treated with glucocorticoids the administration of Ipamorelin counteracted muscle‑strength declines and increased periosteal bone formation rates four‑fold versus glucocorticoid treatment alone ¹. In another rodent study Ipamorelin induced longitudinal bone growth in adult female rats at multiple doses ². Also, pharmacokinetic studies in healthy human volunteers confirmed that Ipamorelin induced a prompt growth hormone peak (≈0.67 h) in a dose‑proportional fashion ³.

Additional animal data suggest Ipamorelin may support gastrointestinal motility and body‑weight gain. In a rodent postoperative‑ileus model Ipamorelin reduced the time to first bowel movement compared to vehicle. In young female rats, chronic Ipamorelin treatment increased body‑weight gain and enhanced basal and stimulated pituitary GH release in vitro, without evidence of desensitisation ^{4, 5}. Taken together, these findings indicate that Ipamorelin increases growth hormone secretion and downstream anabolic and motility effects.

The available human data on Ipamorelin are limited but suggest few serious side effects in short‑term use. In a randomized placebo‑controlled trial involving patients after bowel surgery, adverse events occurred in 87.5 % of the ipamorelin group versus 94.8 % in the placebo group, indicating no significant difference in overall safety in that trial ⁶. Beyond the controlled trial, reports and reviews list injection‑site irritation, increased appetite, nausea, headache, water retention and joint stiffness as reported side‑effects of ipamorelin use in non‑clinical settings. There is very limited long‑term human data, and some animal data suggest that ipamorelin may have adipogenic effects (increasing fat stores) rather than purely anabolic ones ⁷.

Ipamorelin works primarily by acting as a selective agonist at the ghrelin/growth hormone secretagogue receptor known as GHS‑R1a, which is found on cells in the anterior pituitary gland and in other tissues. When Ipamorelin binds GHS‑R1a it triggers a G‑protein‑coupled mechanism (principally Gq/11) that activates phospholipase C (PLC), leading to inositol‑trisphosphate (IP₃) mediated calcium release from intracellular stores and diacylglycerol (DAG) activation of protein kinase C (PKC) ^{8, 9}. The rise in intracellular calcium and PKC activation prompts the exocytosis of growth hormone (GH) from somatotroph cells in a pulsatile manner; this pulsatility has been observed in human pharmacokinetic/pharmacodynamic modelling of GH release after Ipamorelin administration. In addition to stimulating GH release, Ipamorelin’s activation of GHS‑R1a in peripheral tissues contributes to effects on gastrointestinal motility and metabolic regulation as demonstrated in animal models ^{10, 11}. Overall, Ipamorelin’s biological mechanism involves selective GHS‑R1a receptor activation, downstream PLC/IP₃/DAG signalling, intracellular calcium mobilization and GH vesicle release, culminating in pulsatile growth hormone secretion and downstream endocrine and peripheral actions.

The Food and Drug Administration (FDA) has stated there are no FDA‑approved drug products that contain Ipamorelin (free base) or Ipamorelin acetate. On the compounding side: Ipamorelin acetate (and free base) were under consideration in the interim “503A bulks list” for compounding pharmacies, but recent FDA documentation indicates the FDA is proposing that Ipamorelin (free base) and Ipamorelin acetate not be included on the 503A bulks list ¹². In sports, the World Anti‑Doping Agency (WADA) Prohibited List explicitly lists Ipamorelin (along with other GH‑releasing peptides) under S2: “Peptide hormones, growth factors, related substances and mimetics.” ¹³