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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.

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