Animal only
This preclinical study examined whether two ghrelin mimetics (growth hormone secretagogue receptor 1a agonists), anamorelin and ipamorelin, could reduce cisplatin-induced weight loss, appetite suppression, and vomiting in ferrets — an established animal model of chemotherapy-induced nausea and emesis. In isolated ferret ileum tissue, both compounds inhibited electrically-stimulated gut contractions, with anamorelin showing a greater maximum inhibitory effect. When administered intraperitoneally before and after cisplatin, neither compound reduced acute or delayed vomiting episodes, but both reduced associated weight loss by approximately 24% during the late delayed phase (48–72 hours). Strikingly, when anamorelin was delivered directly into the brain (intracerebroventricularly), it reduced acute emesis by approximately 60%, improved food and water intake during the acute phase by roughly 20–40%, and reduced delayed-phase weight loss by approximately 23%. These findings suggest that anamorelin's anti-emetic effects depend on central nervous system penetration rather than peripheral action. Limitations include the use of a single non-human animal species, small group sizes typical of ferret studies, and the invasive intracerebroventricular route, which is not clinically practical. No human data were generated.
Physiology & behavior · Jul 2024DOI ↗ Animal only
This study investigated the effects of ipamorelin acetate (IPA), a synthetic ghrelin agonist, on the reproductive axis of male Mozambique tilapia (Oreochromis mossambicus), a cichlid fish. Fish received either 5 µg or 30 µg of IPA over 21 days and were compared to untreated controls. The study found that IPA administration produced a dose-dependent increase in food intake. Histological analysis revealed significant increases in primary spermatocytes, secondary spermatocytes, and early spermatids in both treatment groups, while the higher dose also increased late spermatids, lobule area, and lumen area. Serum concentrations of luteinizing hormone (LH) and the fish androgen 11-ketotestosterone (11-KT) were significantly elevated in both IPA groups. Androgen receptor protein expression was significantly upregulated in the high-dose group. No significant differences in hypothalamic or pituitary GnRH-immunoreactive fiber density were observed across groups. The authors conclude that ghrelin signaling may promote meiosis-I stage germ cell development through LH stimulation at the pituitary level and 11-KT and androgen receptor activity at the testicular level. Limitations include the use of a single non-mammalian species, a short treatment duration, and the absence of mechanistic pathway confirmation.
Animal reproduction science · Jul 2024DOI ↗ Animal only
This animal study investigated whether ghrelin receptor agonists (ghrelin mimetics) could reduce visceral and somatic pain in the absence of active inflammation. Using a rat model, researchers induced non-inflammatory visceral hypersensitivity by infusing dilute acetic acid into the colon, and somatic mechanical allodynia was also assessed. Two ghrelin receptor agonists were tested: HM01, a centrally and peripherally active compound administered orally, and ipamorelin, a peripherally restricted compound administered intravenously. Pain responses were measured by counting abdominal muscle contractions during colorectal distension (visceral pain) and paw withdrawals to von Frey filament stimulation (somatic pain). The study found that both HM01 and ipamorelin significantly reduced colonic hypersensitivity and somatic allodynia compared to vehicle controls. These effects were reversed by co-administration of the ghrelin receptor antagonist H0900, confirming that the anti-nociceptive effects were receptor-mediated. Notably, the peripherally restricted compound ipamorelin was effective, suggesting peripheral ghrelin receptor activation may be sufficient. The study is limited by its exclusive use of an animal model, meaning translational relevance to humans remains unestablished. The authors propose ghrelin mimetics as a potential novel approach for treating acute visceral and somatic pain.
Journal of experimental pharmacology · Aug 2020DOI ↗ Animal only
This study compared the pharmacokinetics of five peptidyl growth hormone secretagogues — ipamorelin (NNC 26-0161), NNC 26-0194, NNC 26-0235, GHRP-2, and GHRP-6 — in male rats using multiple routes of administration, with a particular focus on nasal delivery. Following intravenous bolus injection, all peptides showed biexponential plasma concentration decline. Ipamorelin stood out with a systemic plasma clearance approximately five times lower than GHRP-6. Excretion routes differed: ipamorelin was primarily cleared via urine, while GHRP-6 and the two NNC peptides were predominantly excreted in bile. Metabolic stability was moderate for ipamorelin and the NNC peptides, with 60–80% of administered doses recoverable as intact peptide from bile and urine combined. Intranasal bioavailability of ipamorelin was estimated at approximately 20%, while NNC 26-0235, NNC 26-0194, and GHRP-2 achieved approximately 50% nasal bioavailability. The authors concluded that nasal delivery appears to be a promising route for this peptide class. Key limitations include exclusive use of animal subjects (male rats), meaning findings may not directly translate to humans, and the study did not assess pharmacodynamic or safety endpoints.
Xenobiotica; the fate of foreign compounds in biological systems · Nov 1998DOI ↗