Prolonged anti-emetic activity and 5-HT3-receptor antagonism by BRL 46470 in conscious ferrets

J Pharm Pharmacol. 1994 Jun;46(6):520-1. doi: 10.1111/j.2042-7158.1994.tb03843.x.

Abstract

The anti-emetic activity of oral and intravenously-administered BRL 46470 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3- dimethyl-indole-1-carboxamide HCl) has been assessed in conscious ferrets. BRL 46470 (0.05-0.5 mg kg-1, p.o.) dose-dependently prevented emesis evoked over a 2 h period by total body X-irradiation. This anti-emetic activity occurred with oral or intravenously-administered BRL 46470 even when dosed 3-4 h before radiation. In conjunction with data obtained in other species, we conclude that BRL 46470 has a potent and long-lasting ability to antagonize actions that are mediated by the 5-HT3 receptor in-vivo.

MeSH terms

  • Administration, Oral
  • Animals
  • Antiemetics / pharmacology*
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Dose-Response Relationship, Drug
  • Ferrets
  • Indoles / pharmacology*
  • Injections, Intravenous
  • Male
  • Serotonin Antagonists / pharmacology*
  • Whole-Body Irradiation

Substances

  • Antiemetics
  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Indoles
  • Serotonin Antagonists
  • BRL 46470