AUTHOR=Rudd John A. , Chan Sze W. , Ngan Man P. , Tu Longlong , Lu Zengbing , Giuliano Claudio , Lovati Emanuela , Pietra Claudio TITLE=Anti-emetic Action of the Brain-Penetrating New Ghrelin Agonist, HM01, Alone and in Combination With the 5-HT3 Antagonist, Palonosetron and With the NK1 Antagonist, Netupitant, Against Cisplatin- and Motion-Induced Emesis in Suncus murinus (House Musk Shrew) JOURNAL=Frontiers in Pharmacology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00869 DOI=10.3389/fphar.2018.00869 ISSN=1663-9812 ABSTRACT=
Ghrelin has well-known activity to stimulate appetite and weight gain. Evidence suggests that ghrelin may also have effects in reducing chemotherapy-induced emesis via growth hormone secretagogue receptors (GHS-R1A) in the brain. However, it is not known whether the stimulation of GHS-R1A has broad inhibitory anti-emetic effects. In the present studies, we used
- The novel orally bioavailable brain-penetrating GHS-R1A agonist, HM01 (1-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-3-methyl-3-[(4R)-1-Methyl-3,3-dimethyl-4-piperidyl]urea), antagonizes motion- and cisplatin-induced emesis.
- HM01 did not reduce emesis induced by nicotine or by intragastric copper sulfate.
- HM01 has positive effects on food consumption after treatment with nicotine.
- HM01 has synergistic effects against cisplatin when combined with palonosetron and palonosetron/netupitant regimens.
- It is suggested that GHS-R1A agonists may be protective against chemotherapy-induced nausea and vomiting in combination with traditional anti-emetics and against motion-induced emesis.