Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret

Br J Cancer. 1990 Jan;61(1):56-60. doi: 10.1038/bjc.1990.12.

Abstract

A new group of selective 5HT3 antagonists are proving to be effective anti-emetics for cytotoxic and radiation induced vomiting in both animal models and man. Current anti-emetic regimens often benefit from combination therapy, in particular the efficacy of metoclopramide (which can be a weak 5HT3 antagonist), can be improved by combination with dexamethasone, another anti-emetic. Hence it was of interest to evaluate whether a 5HT3 receptor antagonist GR38032F could be improved by combination with dexamethasone. Vomiting induced by cyclophosphamide in the ferret was observed after pre-treatment with dexamethasone alone or in combination with GR38032F. Animals were also observed for signs of 'nausea'. Dexamethasone alone proved a weak anti-emetic in this system but did have significant effects on 'nausea'. GR38032F has previously been shown to be capable of totally controlling emesis due to cyclophosphamide in the ferret. Here a dose of GR38032F that is not 100% effective was employed; this was shown to have effects on 'nausea' but most interestingly its anti-emetic action was increased by combination with dexamethasone. This may be important for the minority of patients whose vomiting is not completely controlled by GR38032F alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclophosphamide / adverse effects*
  • Dexamethasone / therapeutic use*
  • Drug Synergism
  • Drug Therapy, Combination
  • Female
  • Ferrets
  • Imidazoles / therapeutic use*
  • Male
  • Ondansetron
  • Serotonin Antagonists*
  • Vomiting / chemically induced
  • Vomiting / drug therapy*

Substances

  • Imidazoles
  • Serotonin Antagonists
  • Ondansetron
  • Dexamethasone
  • Cyclophosphamide