Pargyline-sensitive selective accumulation of a radiolabeled MPTP analog in the primate cerebral cortex and basal ganglia

Synapse. 1990;5(3):207-12. doi: 10.1002/syn.890050306.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / analogs & derivatives*
  • Animals
  • Autoradiography
  • Basal Ganglia / drug effects
  • Basal Ganglia / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Female
  • Haplorhini / metabolism*
  • Image Processing, Computer-Assisted
  • Pargyline / pharmacology*
  • Phosphothreonine / analogs & derivatives*
  • Phosphothreonine / pharmacokinetics
  • Threonine / analogs & derivatives*

Substances

  • 7-mercaptoheptanoylthreonine phosphate
  • Phosphothreonine
  • Threonine
  • Pargyline
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine