Anti-Emetic Effect of Ondansetron and Granisetron after Exposure to Mixed Neutron and Gamma Irradiation

The anti-emetic efficiency of orally administered ondansetron and granisetron has been tested in macaques exposed to a mixed γ and neutron radiation (6 Gy) with a high neutron/γ-ray ratio. Our experiments reveal that a single delivery of ondansetron (1 or <tex-math>$2\ {\rm mg}\ {\rm kg}^{-1}$</tex-math>) or of granisetron (<tex-math>$0.25\ {\rm mg}\ {\rm kg}^{-1}$</tex-math>) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective. Conversely, the delivery of two doses with the same delay prior to and after exposure led to a complete prevention of vomiting and retching. These observations can be explained by the dual mechanism of radiation-induced emesis: an early peripheral mechanism and a later central mechanism. Two deliveries of 5- HT₃ receptor antagonists seem to disrupt serotonergic transmission at the brain stem structures and to affect the peripheral release of serotonin from the gut, thus completely preventing radiation-induced vomiting. This study confirms that the <tex-math>$5\text{-}{\rm HT}_{3}\text{-dependent}$</tex-math> mechanisms that mediate emesis are similar for both neutron and γ radiation.