Distribution of 1-methyl-4-phneyl-1,2,3,6-tetrahydropyridine in experimental animals studied by positron emission tomography and whole body autoradiography
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a selective potent neurotoxin which has induced a syndrome similar to parkinsonism both in man and in monkeys. At autopsy degeneration of pigmented nerve cells in the pars compacta of the substantia nigra has been confirmed. The regional distribution of intravenously administered 1-(/sup 11/C-methyl)-4-phenyl-1,2,3,6-tetrahydropyridine (/sup 11/C-MPTP) in the brain of Rhesus monkeys was studied by positron emission tomography and the whole body distribution in mice was documented by autoradiography and by impulse counting of selected tissues. A rapid and high uptake of /sup 11/C-MPTP derived radioactivity was seen in areas corresponding to striatum and midbrain, including the substantia nigra area. Pretreatment of the monkey with spiperone, a selective dopamine receptor antagonist, did not alter uptake nor the kinetics of the /sup 11/C-MPTP derived radioactivity. Thus, /sup 11/C-MPTP does not have a high affinity for postsynaptic dopamine receptors. A remarkably high uptake of /sup 11/C-MPTP derived radioactivity was seen in the eye of the monkey. The selective uptake of radioactivity in the eye was also confirmed in pigmented but not in albino mice. The melanin affinity of MPTP may cause high intracellular concentrations of the compound or its metabolites in the melanin containing nerve cells in substantia nigra, which may explain the serious vulnerability of these neurons to MPTP. 30 references, 3 figures, 2 tables.
- Research Organization:
- Uppsala Univ., Sweden
- OSTI ID:
- 6425572
- Journal Information:
- Life Sci.; (United States), Vol. 38:1
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
DOPAMINE
RECEPTORS
PYRIDINE
BIOCHEMICAL REACTION KINETICS
TISSUE DISTRIBUTION
AFFINITY
AUTORADIOGRAPHY
CARBON 11
EMISSION COMPUTED TOMOGRAPHY
EXPERIMENTAL DATA
EYES
LABELLED COMPOUNDS
MELANIN
METABOLITES
MONKEYS
NERVE CELLS
TOXINS
TRACER TECHNIQUES
UPTAKE
AMINES
ANIMAL CELLS
ANIMALS
ANTIGENS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AZINES
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
BODY AREAS
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
COMPUTERIZED TOMOGRAPHY
DATA
DIAGNOSTIC TECHNIQUES
DISTRIBUTION
DRUGS
EVEN-ODD NUCLEI
FACE
HEAD
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INFORMATION
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MATERIALS
MINUTES LIVING RADIOISOTOPES
NEUROREGULATORS
NUCLEI
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PHENOLS
PIGMENTS
POLYPHENOLS
PRIMATES
PYRIDINES
RADIOISOTOPES
REACTION KINETICS
SENSE ORGANS
SOMATIC CELLS
SYMPATHOMIMETICS
TOMOGRAPHY
TOXIC MATERIALS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550201 - Biochemistry- Tracer Techniques