Regional cerebral pharmacokinetics of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as examined by positron emission tomography in a baboon is altered by tranylcypromine

Stephen M. Moerlein, Gerhard Stöcklin, Günter Pawlik, Klaus Wienhard, Wolf Dieter Heiss

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Abstract

The selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has chemical and metabolic characteristics which allow its in vivo tissue distribution to be studied using positron emission tomography (PET). The cerebral pharmacokinetics of [11C]MPTP labelled at the N-methyl position was quantitatively traced in the living brain of an anesthetized baboon using PET, and the effect of administration of the monoamine oxidase (MAO) inhibitor tranylcypromine on this regional cerebral distribution was determined in the same animal. Following injection of [11C]MPTP, radioactivity rapidly concentrated in the basal ganglia of the primate's brain. This in vivo localization was prevented by prior administration of tranylcypromine, suggesting that it is oxidized metabolites of MPTP which are sequestered by dopaminergic neurons. Radioactivity rapidly localized preferentially in the basal ganglia of the primate brain, and this in vivo localization was blocked by prior administration of the MAO inhibitor tranylcypromine.

Original languageEnglish
Pages (from-to)205-209
Number of pages5
JournalNeuroscience Letters
Volume66
Issue number2
DOIs
StatePublished - May 15 1986

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • MPTP
  • Papio anubis
  • dopaminergic neuron
  • neurotoxin
  • positron emission tomography PET
  • tranylcypromine

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