Dexamethasone can potentiate the anti-emetic action of a 5HT3 receptor antagonist on cyclophosphamide induced vomiting in the ferret.
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.
Hawthorn
J
J
Department of Physiology, St Georges Hospital Medical School, London, UK.
Cunningham
D
D
D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects*; D003907:Dexamethasone / Q000627:therapeutic use*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005289:Ferrets; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D017294:Ondansetron; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D003907:Dexamethasone; D003520:Cyclophosphamide