Urinary excretion of MPTP and its primary metabolites in mice.
Mice were injected with single doses of MPTP (15 mg/kg, s.c.) containing one microCi of [3H]methyl-MPTP. Approximately 42% of the total injected [3H] was detected in the urine within 3 hours after drug administration. The early urine samples were analyzed using high pressure liquid chromatography. MPTP N-oxide was identified as a major metabolite, with trace amounts of MPP+ and MPTP also detected. The urinary volume and excretion of MPTP metabolites were inhibited by pretreating the animals with probenecid (250 mg/kg, i.p.). These results indicate that large amounts of injected MPTP are rapidly metabolized in the periphery by liver enzymes to form MPTP N-oxide.
Lau
Y S
YS
Department of Pharmacology, Creighton University, Omaha, NE 68178.
Crampton
J M
JM
Wilson
J A
JA
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011339:Probenecid / Q000494:pharmacology; D011725:Pyridines / Q000493:pharmacokinetics / Q000652:urine*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D011339:Probenecid