2-MERCAPTO-PROPYLARNINE - RADIOPHARMACOLOGY IN MICE, PHARMACOKINETIC STUDIES IN MICE AND IN RATS, MUTAGENICITY AND DIFFERENTIAL DISTRIBUTION BETWEEN TISSUES AND EMT6 TUMOR IN MICE

Radiopharmacological studies conducted with 2-mercapto-propylamine (2M PA), a methylated derivative of cysteamine, indicated a good efficienc y in while body irradiated mice as observed over a period of 9 months. Its efficacy was also checked for supralethal irradiations of restric ted body parts: in the brain and the rectum. The diffusion of C-14-lab elled 2MPA was assessed by an autoradiographic study and measurement o f its distribution in the main organs in mice. 2MPA penetrated the blo od br ain barrier but concentrated preferentially in the liver, kidney and skin. Fixation on plasmatic proteins was much lower in rats than in mice but urinary and faecal eliminations were of the same order for the two species. An important biliary excretion of 2MPA or its metabo lites in rats combined with their lack in the faeces underlies an ente ro-hepatic cycle. A differential diffusion of 2MPA between normal tiss ues in mice and EMT6 rumours was clearly revealed by autoradiographic observations. The ability of 2MPA to trap 2,2'-diphenyl 1-picryl hydra zyl, an organic free radical, was checked by in vitro studies. Its per formance indicated that 2MPA acted at least as a free radical scavenge r. Ames test demonstrated that 2MPA whatever the dose employed was not a mutagenic agent. Pharmacological and pharmacokinetical observations provided a better understanding of the activity of this drug. (C) 199 8 Elsevier Science S.A. All rights reserved.