The antiemetic profile of Y-25130, a new selective 5-HT3 receptor antagonist

Eur J Pharmacol. 1991 Apr 24;196(3):299-305. doi: 10.1016/0014-2999(91)90443-t.

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-HT3 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-25130, 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-25130 may become an effective antiemetic drug against emesis induced by anticancer therapy.

MeSH terms

  • Animals
  • Antiemetics / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Cisplatin / adverse effects
  • Cyclophosphamide / administration & dosage
  • Dogs
  • Doxorubicin / administration & dosage
  • Ferrets
  • Kinetics
  • Oxazines / pharmacology*
  • Radioligand Assay
  • Receptors, Neurotransmitter / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin / pharmacology
  • Serotonin Antagonists*
  • Time Factors
  • Vomiting / chemically induced
  • Vomiting / drug therapy
  • Whole-Body Irradiation / adverse effects

Substances

  • Antiemetics
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Oxazines
  • Receptors, Neurotransmitter
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • azasetron
  • Doxorubicin
  • Cyclophosphamide
  • Cisplatin