Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia.
The distribution of radioiodinated N-methyl-4-(4-hydroxy-3-iodobenzyl)-1,2,3,6-tetrahydropyridine (MHTP), an analog of the reportedly nontoxic N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, (4-homo-MPTP), has been studied in the primate. [123I]MHTP-derived radioactivity exhibited a progressive accumulation and prolonged retention within the primate eye. Following iv injection, [123I]MHTP rapidly accumulated within the primate brain and was subsequently oxidized to a radiolabeled metabolite. The half-life of [123I]MHTP-derived radioactivity within the primate brain was 50 min. The highest concentrations of radioactivity were found in the caudate-putamen and the frontal, temporal and cingulate cortices; the substantia nigra and inferior olivary nucleus were labeled with medium intensity. Very low concentrations of radiolabel were detected in the cerebellum and white matter. Selective accumulation of [125I]MHTP-derived radioactivity within these structures was blocked by pretreatment with pargyline, suggesting that monoamine oxidase B is involved in the bioactivation of radioiodinated MHTP.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis.
Kung
H F
HF
Mash
D C
DC
Jabir
M
M
Billings
J
J
Pablo
J
J
Dutta
A
A
Freshler
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000818:Animals; D001345:Autoradiography; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D000882:Haplorhini / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D010293:Pargyline / Q000494:pharmacology*; D010769:Phosphothreonine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013912:Threonine / Q000031:analogs & derivatives*
C049349:7-mercaptoheptanoylthreonine phosphate; D010769:Phosphothreonine; D013912:Threonine; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine