5-HT3 receptor antagonists ameliorate emesis in the ferret evoked by neutron or proton radiation

Nausea and vomiting produced by sub-lethal doses of X- or gamma-rays can be ameliorated by serotonin subtype-three (5-hydroxytryptamine; 5-HT3) receptor antagonists. The effectiveness of these anti-emetics on blocking the emetic responses induced by fission neutron or proton radiation exposure was evaluated in the ferret animal model.

5-HT3 receptor antagonists or bilateral vagotomy will ameliorate that emesis evoked by fission neutrons or protons.

Groups of ferrets were exposed to whole-body or head-shielded radiations of varying qualities: fission spectrum neutons, high-energy protons, or gamma-rays. Prior to that exposure, some groups were either vagotomized or received subcutaneous (s.c.) or oral (p.o.) treatment with various doses of the 5-HT3 receptor antagonist antiemetics eusatron and ondansetron.

We demonstrated that both eusatron and ondansetron effectively abolished the emesis normally induced by 2-Gy doses of either 60Co gamma or neutron:gamma, mixed-field irradiation, the latter with a neutron-to-total dose ratio (Dn/Dt) of 0.9+/-2% (%SD). Different routes of delivery of the anti-emetics yielded different degrees of inhibition of the emetic responses; p.o. treatment was less efficacious than s.c. treatment for the emesis to fission neutrons. Eusatron was significantly more effective than ondansetron on a mg x kg(-1) basis. Bilateral vagotomy also attenuated or abolished the emetic responses to the mixed-field neutron exposures. Furthermore, emesis induced by exposure to 2.5 Gy of 200-MeV protons was effectively abolished by ondansetron.

These results are consistent with the concept that similar physiological and pharmacological mechanisms underlie the emetic responses to different qualities of radiation.