Evaluation of domperidone as a modifier of gamma-radiation-induced emesis

The D2 antidopaminergic drug domperidone was evaluated, singly and in combination with synthetic adrenocorticoid and an H2 antihistamine, for its ability to reduce the acute emetic effects of 60Co whole-body radiation. Random-source adult male dogs were fasted 12 hr, fed a standard meal, injected 44 min later, and irradiated 47 min after that. Four groups of dogs were irradiated after drug injections as follows: saline (Con), domperidone (Dom), cimetidine + thiethylperazine (Cim + Thi), and dexamethasone + domperidone + cimetidine (Dex + Dom + Cim). Drug quantities given the dogs represented 10 mg Dom, 10 mg Thi, 20 mg Dex, and 300 mg Cim for an average human (70 kg, 1.8 m2). Subjects were exposed on an up-down schedule to determine the radiation necessary to produce vomiting in 50% (ED50) of each group. Emesis onset and offset times and number of episodes were recorded. The Dom group had more emetic episodes than any other. The Dex + Dom + Cim combination significantly raised the emetic threshold while maintaining episodes at a low incidence.