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.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro laboratory study.
PubMed 39043357 · doi:10.1016/j.physbeh.2024.114644
What was done
Researchers evaluated the growth hormone secretagogue receptor 1a agonists anamorelin and ipamorelin in ferret models of cisplatin-induced toxicity. In vitro, their ability to inhibit electrical field stimulation (EFS)-induced contractions was tested in isolated ferret ileum. In vivo, ferrets received intraperitoneal (i.p.) anamorelin (1–3 mg/kg), ipamorelin (1–3 mg/kg), or vehicle 30 seconds before cisplatin (5 mg/kg, i.p.) and every 24 hours thereafter, with emetic behavior, food, and water intake monitored for 72 hours. Anamorelin (10 µg) was also tested via intracerebroventricular (i.c.v.) administration.
What was found
In isolated ileum, anamorelin and ipamorelin inhibited EFS-induced contractions by 94.4% (IC50 = 14.0 µM) and 54.4% (IC50 = 11.7 µM), respectively. Systemic (i.p.) administration of either agonist did not reduce acute or delayed emesis, but both decreased cisplatin-associated weight loss during the delayed phase (48–72 hours) by approximately 24%. Intracerebroventricular anamorelin reduced acute emesis by 60% (no effect on delayed emesis), improved acute-phase food and water intake by approximately 20% to 40%, and reduced delayed-phase weight loss by ~23%.
Why it matters
The findings demonstrate that ghrelin receptor agonists can alleviate chemotherapy-induced weight loss, but suggest anamorelin requires central nervous system penetration to exert anti-emetic actions.
Limits
This is an animal and tissue study; exact animal sample sizes and variance metrics were omitted from the abstract. Results in ferrets may not fully translate to human chemotherapy-induced nausea, vomiting, or cachexia.
Cited by
- supports CJC-1295 is a growth hormone-releasing hormone derivative and Ipamorelin is a ghrelin receptor agonist that synergistically stimulate growth hormone release.