Prevention and treatment of the gastric symptoms of radiation sickness.
Currently available treatments for radiation-induced nausea and vomiting either are ineffective or reduce performance. The new antiemetic and gastrokinetic agent zacopride was tested in rhesus monkeys to assess its behavioral toxicity and its ability to inhibit radiation-induced emesis. Zacopride (intragastric, 0.3 mg/kg) or a placebo was given blindly and randomly in the basal state and 15 min before a whole-body 800 cGy 60Co gamma-radiation dose (except for the legs which were partially protected to permit survival of some bone marrow). We determined (1) gastric emptying rates; (2) the presence and frequency of retching and vomiting; and (3) the effect of zacopride on the performance of a visual discrimination task in nonirradiated subjects. No vomiting, retching, or decreased performance was observed after either placebo or zacopride in the control state. Following irradiation plus placebo, 70 emeses were observed in 5 of 6 monkeys, and 353 retches were observed in all 6 monkeys. In contrast, only 1 emesis was observed in 1 of 6 monkeys and 173 retches were seen in 4 of 6 monkeys after irradiation plus zacopride (P less than 0.01). Zacopride also significantly inhibited radiation-induced suppression of gastric emptying. When given after the first vomiting episode in a separate group of irradiated monkeys, zacopride completely prevented any subsequent vomiting. The present results demonstrate that intragastric administration of zacopride significantly inhibited radiation-induced retching, vomiting, and suppression of gastric emptying in rhesus monkeys and did not cause detectable behavioral side effects when given to nonradiated monkeys. This observation has important implications in the treatment of radiation sickness.
Dubois
A
A
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Fiala
N
N
Boward
C A
CA
Bogo
V
V
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D004192:Discrimination, Psychological / Q000187:drug effects; D005767:Gastrointestinal Diseases / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D008253:Macaca mulatta; D008297:Male; D011833:Radiation Injuries, Experimental / Q000150:complications*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; C055971:zacopride