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Influence of monoamine oxidase inhibitors and a dopamine uptake blocker on the distribution of 11 C‐N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, 11 C‐MPTP, in the head of the Rhesus monkey
Author(s) -
Hartvig P.,
Larsson B. S.,
Lindberg B. S.,
Oreland L.,
Gullberg P.,
Långström B.,
Rimland A.,
Lundqvist H.,
Malmborg P.,
Lindquist N. G.
Publication year - 1986
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/j.1600-0404.1986.tb04618.x
Subject(s) - monoamine oxidase , mptp , dopamine , chemistry , monoamine oxidase b , pharmacology , medicine , enzyme , biochemistry , dopaminergic
N‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine, MPTP, is a neurotoxic substance known to induce a parkinsonian syndrome in primates. The distribution of intravenously injected 11 C‐labelled MPTP ( 11 C‐MPTP) in the head of Rhesus monkeys was studied by means of positron emission tomography, PET. The influence of pretreatment with two monoamine oxidase (MAO) inhibitors, namely pargyline and clorgyline, and a dopamine uptake blocker, nomifensine, on the distribution was also evaluated. The 11 C‐radioactivity was taken up in all brain regions and maximum radioactivities were found 3‐8 min after intravenous administration of MPTP. The 11 C‐MPTP‐derived radioactivity showed a constant value throughout the study period in areas corresponding to the striatum and mesencephalon in monkeys not pretreated and in monkeys pretreated with clorgyline and with nomifensine. Pargyline pretreatment, however, resulted in consecutive elimination of 11 C‐MPTP‐derived radioactivity from the different brain regions with half‐lives of 40‐60 min. The total radioactivity in blood was also higher after pargyline pretreatment indicating successful inhibition of metabolism. The eyes and temporal muscle each showed radioactivity values of the same order in all monkeys irrespective of pretreatment. The results support findings by other authors that MPTP was rapidly converted in the brain to a reactive metabolite which concentration remained constant in the brain during the PET study. Pargyline in the dosage used is known to be a non‐selective MAO inhibitor and it prevented the metabolism of 11 C‐MPTP to the products retained in the brain. Clorgyline, a MAO inhibitor of Type A, did not inhibit this conversion. Nomifensine may have inhibited the active uptake into dopaminergic neurons, although such an effect could not be observed with PET.