Anamorelin: An Oral Ghrelin Agonist That Boosts Appetite and Growth Hormone in Animals
Anamorelin, an oral ghrelin receptor agonist, dose-dependently increased food intake, body weight, and growth hormone in rats and pigs, supporting its development for cancer cachexia.
Quick Facts
What This Study Found
Anamorelin (ANAM) is a potent, orally active ghrelin receptor agonist that significantly increased food intake, body weight, and growth hormone levels in rats at doses of 3, 10, and 30 mg/kg over 6 days. The effects were dose-dependent, with GH increases reaching significance at 10 and 30 mg/kg.
In pigs, both single-dose (3.5 mg/kg) and continuous dosing (1 mg/kg/day) increased growth hormone and IGF-1 levels. In vitro, ANAM showed strong binding affinity and agonist activity at the ghrelin receptor and stimulated GH release from rat pituitary cells. These results established ANAM as a highly specific ghrelin receptor agonist with appetite-stimulating and anabolic properties.
Key Numbers
3, 10, 30 mg/kg doses in rats · 6-day oral dosing · dose-dependent food intake and BW increases · 3.5 mg/kg single dose and 1 mg/kg/day continuous in pigs · GH + IGF-1 increases confirmed
How They Did This
In vitro: binding assays and fluorescent imaging plate reader assays in HEK293 and BHK cells to measure ghrelin receptor affinity and agonist activity. GH release was measured in rat pituitary cells. In vivo: rats received oral ANAM at 3, 10, or 30 mg/kg daily for 6 days to track food intake and body weight, with single doses to assess GH response. Pigs received single or continuous ANAM doses to evaluate GH and IGF-1 responses.
Why This Research Matters
Cancer cachexia — the severe muscle wasting and weight loss seen in many cancer patients — kills an estimated 20% of cancer patients and has no widely effective treatment. An oral ghrelin agonist that can increase appetite, body weight, and growth hormone levels could address this unmet need. Anamorelin's oral bioavailability is particularly important, since cachexia patients often struggle with injections.
The Bigger Picture
Cancer cachexia remains one of the most difficult complications in oncology, contributing to poor quality of life and reduced survival. Anamorelin went on to reach Phase III clinical trials (ROMANA studies) after this preclinical work, making it one of the most advanced ghrelin agonists in development. This paper provides the foundational pharmacology that supported that clinical progression.
What This Study Doesn't Tell Us
This is a preclinical pharmacology study in rats and pigs — the results describe the drug's profile before human trials. Cancer cachexia models were not used; the animals were healthy, so the appetite and weight effects may differ in disease states. Long-term safety and efficacy in cancer patients require clinical trial data.
Questions This Raises
- ?Does anamorelin's appetite-stimulating effect translate to meaningful weight gain and quality of life improvement in cancer cachexia patients?
- ?Can anamorelin preserve lean muscle mass specifically, or does it primarily increase fat mass?
- ?How does long-term ghrelin receptor activation affect tumor growth — is there a safety concern?
Trust & Context
- Key Stat:
- Oral + dose-dependent Anamorelin increased food intake and body weight at all three dose levels tested in rats (3, 10, 30 mg/kg) — critically, it works as an oral pill
- Evidence Grade:
- This is a well-characterized preclinical study with in vitro receptor binding data, in vivo dose-response in two species (rats and pigs), and multiple endpoints. However, it predates clinical trials and uses healthy animals rather than cancer cachexia models.
- Study Age:
- Published in 2014 in the Journal of Cachexia, Sarcopenia and Muscle. Anamorelin has since progressed through Phase III trials (ROMANA-1 and ROMANA-2), making this foundational preclinical paper an important part of its development history.
- Original Title:
- Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.
- Published In:
- Journal of cachexia, sarcopenia and muscle, 5(4), 329-37 (2014)
- Authors:
- Pietra, Claudio(7), Takeda, Yasuhiro(3), Tazawa-Ogata, Naoko, Minami, Masashi, Yuanfeng, Xia, Duus, Elizabeth Manning, Northrup, Robert
- Database ID:
- RPEP-02474
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is cancer cachexia and why is it hard to treat?
Cancer cachexia is severe muscle wasting and weight loss caused by cancer. It affects up to 80% of advanced cancer patients and contributes to roughly 20% of cancer deaths. Simply eating more doesn't fix it because the wasting is driven by metabolic changes from the tumor. An oral drug that stimulates appetite and growth hormone could address multiple aspects of the syndrome.
How is anamorelin different from natural ghrelin?
While both activate the same receptor, anamorelin can be taken as a pill — natural ghrelin must be injected and is rapidly broken down in the body. Anamorelin is also more selective and has a longer duration of action, making it more practical as a daily medication for cachexia patients.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-02474APA
Pietra, Claudio; Takeda, Yasuhiro; Tazawa-Ogata, Naoko; Minami, Masashi; Yuanfeng, Xia; Duus, Elizabeth Manning; Northrup, Robert. (2014). Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.. Journal of cachexia, sarcopenia and muscle, 5(4), 329-37. https://doi.org/10.1007/s13539-014-0159-5
MLA
Pietra, Claudio, et al. "Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist, for the treatment of cancer anorexia-cachexia syndrome: preclinical profile.." Journal of cachexia, 2014. https://doi.org/10.1007/s13539-014-0159-5
RethinkPeptides
RethinkPeptides Research Database. "Anamorelin HCl (ONO-7643), a novel ghrelin receptor agonist,..." RPEP-02474. Retrieved from https://rethinkpeptides.com/research/pietra-2014-anamorelin-hcl-ono7643-a
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.