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Digitale Medien

Effects of l-Methyl-4-Phenyl-l,2,3,6-Tetrahydropyridine in the Dog: Effect of Pargyline Pretreatment (1989)

Johannessen, J. N. ; Chiueh, C. C. ; Bacon, J. P. ; [weitere]

Oxford, UK : Blackwell Publishing Ltd

Journal of neurochemistry 53 (1989), S. 0

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ISSN: 1471-4159

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Medizin

Notizen: Abstract: Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c, twice), with pargyline alone, or were unin-jected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine β-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the ni-grostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectively in aminergic terminals.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1111/j.1471-4159.1989.tb07373.x

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Digitale Medien

Neurotoxic damage to the nigrostriatal system in rats following intranigral administration of MPDP+ and MPP+ (1988)

Sun, C. J. ; Johannessen, J. N. ; Gessner, W. ; [weitere]

Springer

Journal of neural transmission 74 (1988), S. 75-86

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ISSN: 1435-1463

Schlagwort(e): MPTP ; MPDP+ ; MPP+ ; substantia nigra ; nigrostriatal neurons ; neurotoxin ; dopamine

Quelle: Springer Online Journal Archives 1860-2000

Thema: Medizin

Notizen: Summary Unilateral intranigral administration of the oxidative metabolites of 1-methyl-4-pheny1-1,2,3,6-tetrahydropyridine (MPTP), 1-methyi-4-phenyl-dihydropyridine (MPDP+) or l-methyl-4-phenylpyridine (MPP+) produced dose-dependently a depletion of dopamine in the ipsilateral striatum of rats two weeks following treatment.d- Amphetamine and apomorphine induced circling toward the lesioned side in these unilaterally treated animals. No contralateral circling behavior was observed after challenging with apomorphine. This dopamine lesioning effect of MPP+ was not blocked by pretreatment of animals with a dopamine uptake blocker, GBR 12909. Furthermore, MPP+ increased the45Ca accumulation into cells at the site of injection and produced “nonspecific” cell membrane and/or cytotoxic damage seen by histological procedures. These results indicate that MPDP+ and MPP+ produced localized cytotoxic damage to nigrostriatal neurons, caused a decrease in striatal dopamine, and disrupted the nigrostriatal system's functioning following intranigral administration to rats. It is postulated that the cationic surfactant properties of MPDP+ and MPP+ might contribute to its neurotoxic effects.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1007/BF01245141

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Digitale Medien

Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism (1984)

Markey, S. P. ; Johannessen, J. N. ; Chiueh, C. C. ; [weitere]

[s.l.] : Nature Publishing Group

Nature 311 (1984), S. 464-467

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ISSN: 1476-4687

Quelle: Nature Archives 1869 - 2009

Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik

Notizen: [Auszug] Radiolabelled [1-14C]MPTP was prepared by reacting 14C-methyl iodide (2 mCi, 5.4 mg) with 4-phenylpyridine (10 mg) in dichloromethane at room temperature for 24 h, followed by reduction of the dried residue in aqueous solution with excess NaBH4, using the method of Lyle6. The product, [1-14C]MPTP, ...

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1038/311464a0

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Digitale Medien

Efficient extraction and mass spectrometric assay of serotonin in biological fluids (1981)

Markey, S. P. ; Colburn, R. W. ; Johannessen, J. N.

Chichester : Wiley-Blackwell

Biological Mass Spectrometry 8 (1981), S. 301-304

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ISSN: 1052-9306

Schlagwort(e): Chemistry ; Analytical Chemistry and Spectroscopy

Quelle: Wiley InterScience Backfile Collection 1832-2000

Thema: Chemie und Pharmazie

Notizen: A gas chromatographic mass spectrometric assay for serotonin (5-hydroxytryptamine) has been developed. Serotonin is acylated in homogenized biological media, efficiently extracted into ethyl acetate, and further derivatized with pentafluoropropionic anhydride. Mass spectral characterization of derivatized serotonin using electron and positive or negative chemical ionization indicates that electron ionization mass spectrometry is useful for serotonin assay in most biological fluids and tissues, but that electron capture negative chemical ionization is required for samples containing less than 1-2 ng (cerebrospinal fluid). An assay limit of 10 pg per sample has been established. Examples of applications for the assay of serotonin in human platelets, rat spinal cord, and monkey cerebrospinal fluid are presented.

Zusätzliches Material: 2 Ill.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1002/bms.1200080704

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