2-Mercapto-propylamine: radiopharmacology in mice, pharmacokinetic studies in mice and in rats, mutagenicity and differential distribution between tissues and EMT6 tumour in mice.
Radiopharmacological studies conducted with 2-mercapto-propylamine (2MPA), a methylated derivative of cysteamine, indicated a good efficiency in whole body irradiated mice as observed over a period of 9 months. Its efficacy was also checked for supralethal irradiations of restricted body parts: in the brain and the rectum. The diffusion of 14C-labelled 2MPA was assessed by an autoradiographic study and measurement of its distribution in the main organs in mice. 2MPA penetrated the blood brain 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 metabolites in rats combined with their lack in the faeces underlies an entero-hepatic cycle. A differential diffusion of 2MPA between normal tissues in mice and EMT6 tumours was clearly revealed by autoradiographic observations. The ability of 2MPA to trap 2,2'-diphenyl 1-picryl hydrazyl, an organic free radical, was checked by in vitro studies. Its performance indicated that 2MPA acted at least as a free radical scavenger. 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.
Schumacher
C P
CP
Laboratoire de Chimie Organique Pharmaceutique, Faculté de Pharmacie, Montpellier, France.
Robbe
Y
Y
Sicart
M T
MT
Subra
G
G
Delard
R
R
Dubois
J B
JB
D000818:Animals; D001921:Brain / Q000528:radiation effects; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009152:Mutagenicity Tests; D009374:Neoplasms, Experimental / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000528:radiation effects; D013438:Sulfhydryl Compounds / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution
C112396:2-mercapto-propylamine; D011837:Radiation-Protective Agents; D013438:Sulfhydryl Compounds