Prolonged anti-emetic activity and 5-HT3-receptor antagonism by BRL 46470 in conscious ferrets.
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.
Bermudez
J
J
SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK.
Sanger
G J
GJ
D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D007211:Indoles / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014916:Whole-Body Irradiation
D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D012702:Serotonin Antagonists; C075685:BRL 46470