The growth hormone secretagogue receptor 1a agonists, anamorelin and ipamorelin, inhibit cisplatin-induced weight loss in ferrets: Anamorelin also exhibits anti-emetic effects via a central mechanism.
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.
Why this grade: All experiments were conducted exclusively in ferrets and isolated ferret tissue, with no human participants or clinical data, making this animal-only evidence.
This study investigated whether ghrelin mimetics, namely anamorelin and ipamorelin, can alleviate weight loss and inhibition of feeding observed during acute and delayed phases of cisplatin-induced emesis in ferrets. The potential of anamorelin to inhibit electrical field stimulation (EFS)-induced contractions of isolated ferret ileum was compared with ipamorelin. In other experiments, ferrets were administered anamorelin (1-3 mg/kg), ipamorelin (1-3 mg/kg), or vehicle intraperitoneally (i.p.) 30 s before cisplatin (5 mg/kg, i.p.) and then every 24 h, and their behaviour was recorded for up to 72 h. Food and water consumption was measured every 24 h. The effect of anamorelin (10 µg) was also assessed following intracerebroventricular administration. Anamorelin and ipamorelin inhibited EFS-induced contractions of isolated ileum by 94.4 % (half-maximal inhibitory concentration [IC 50 ]=14.0 µM) and 54.4 % (IC 50 =11.7 µM), respectively. Neither of compounds administered i.p. had any effect on cisplatin-induced acute or delayed emesis, but both inhibited associated cisplatin-induced weight loss on the last day of delayed phase (48-72 h) by approximately 24 %. Anamorelin (10 µg) administered intracerebroventricularly reduced cisplatin-induced acute emesis by 60 % but did not affect delayed emesis. It also improved food and water consumption by approximately 20 %-40 % during acute phase, but not delayed phase, and reduced associated cisplatin-induced weight loss during delayed phase by ∼23 %. In conclusion, anamorelin and ipamorelin administered i.p. had beneficial effects in alleviating cisplatin-induced weight loss during delayed phase, and these effects were seen when centrally administered anamorelin. Anamorelin inhibited cisplatin-induced acute emesis following intracerebroventricular but not intraperitoneal administration, suggesting that brain penetration is important for its anti-emetic mechanism of action.
Educational summary of published research — not medical advice. Full text is shown only where licensing permits.