Study summary · research use only
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
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this ferret study, the authors tested whether the ghrelin mimetics anamorelin and ipamorelin could reduce weight loss and feeding inhibition during cisplatin-induced emesis. Anamorelin and ipamorelin inhibited electrical field stimulation-induced contractions of isolated ferret ileum by 94.4 % (IC50=14.0 µM) and 54.4 % (IC50=11.7 µM), respectively. Neither compound given intraperitoneally at 1-3 mg/kg affected cisplatin (5 mg/kg)-induced acute or delayed emesis, but both reduced associated weight loss during the delayed phase by approximately 24 %. Anamorelin given intracerebroventricularly at 10 µg reduced acute emesis by 60 % without affecting delayed emesis, improved food and water consumption by approximately 20 %-40 % during the acute phase, and reduced delayed-phase weight loss by ∼23 %. The authors state brain penetration appears important for anamorelin's anti-emetic mechanism.
Abstract
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 [IC50]=14.0 µM) and 54.4 % (IC50=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.
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