ANTIEMETIC EFFECT OF ONDANSETRON AND GRANISETRON AFTER EXPOSURE TO MIXED NEUTRON AND GAMMA-IRRADIATION

The anti-emetic efficiency of orally administered ondansetron and gran isetron has been tested in macaques exposed to a mixed gamma and neutr on radiation (6 Gy) with a high neutron/gamma-ray ratio. Our experimen ts reveal that a single delivery of ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective. Conversely, the deliv ery of two doses with the same delay prior to and after exposure led t o a complete prevention of vomiting and retching. These observations c an be explained by the dual mechanism of radiation-induced emesis: an early peripheral mechanism and a later central mechanism. Two deliveri es of 5-HT3 receptor antagonists seem to disrupt serotonergic transmis sion at the brain stem structures and to affect the peripheral release of serotonin from the gut, thus completely preventing radiation-induc ed vomiting. This study confirms that the 5-HT3-dependent mechanisms t hat mediate emesis are similar for both neutron and gamma radiation. ( C) 1998 by Radiation Research Society.