The antiemetic profile of Y-25130, a new selective 5-HT 3 receptor antagonist

Abstract

Y-25130 ((±)N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride) is a potent and selective 5-HT 3 receptor antagonist free of dopamine receptor blocking activity. This compound was effective against emesis induced in animals by cytotoxic drugs or by total body X-radiation. When given prophylactically, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. Y-2S130, at the dose of 0.3 mg/kg i.v., almost completely inhibited X-radiation-induced emesis in ferrets. When given during emesis, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin- and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. The i.v. dose of 0.3 mg/kg of Y-25130 was enough to almost completely inhibit cisplatin-induced emesis in dogs for 24 h. From these results, it is suggested that Y-2S130 may become an effective antiemetic drug against emesis induced by anticancer therapy.