title: Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia.
abstract: 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.
authors.affiliation: Department of Radiology, University of Minnesota, Minneapolis.
authors.forename: S M
authors.initials: SM
authors.lastname: Efange
authors.forename: H F
authors.initials: HF
authors.lastname: Kung
authors.forename: D C
authors.initials: DC
authors.lastname: Mash
authors.forename: M
authors.initials: M
authors.lastname: Jabir
authors.forename: J
authors.initials: J
authors.lastname: Billings
authors.forename: J
authors.initials: J
authors.lastname: Pablo
authors.forename: A
authors.initials: A
authors.lastname: Dutta
authors.forename: A
authors.initials: A
authors.lastname: Freshler
mesh_terms: 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*
chemical_list: C049349:7-mercaptoheptanoylthreonine phosphate; D010769:Phosphothreonine; D013912:Threonine; D010293:Pargyline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine