Advances in Our Understanding of the Mechanisms of the Neurotoxicity of MPTP and Related Compounds

The discovery that 1 -methyl4-phenyl1,2,3,6-tetrahydropyndine (MPTP), a contaminant of a synthetic pethidine analogue sold as a street drug, produced a condition resembling Parkinson’s disease has been described in detail (for reviews, see Langston, 1985; Snyder and DAmato, 1986). MPTP was shown to cause a selective destruction of nigrostriatal dopaminergic neurons in primates and some other animal species, and this stimulated a great deal ofwork on the mechanisms involved in its neurotoxic effects and their possible relationship to idiopathic Parkinson’s disease. Earlier work on the mechanism by which MPTP exerts its selective neurotoxic effects has been reviewed before, and the present account will concentrate on more recent discoveries concerning its biochemical actions and the unresolved problems that remain.

[1]  J. Reinhard,et al.  Energy-driven uptake of the neurotoxin 1-methyl-4-phenylpyridinium into chromaffin granules via the catecholamine transporter. , 1988, The Journal of biological chemistry.

[2]  M. Naoi,et al.  Novel toxins and Parkinson's disease: N-methylation and oxidation as metabolic bioactivation of neurotoxin. , 1994, Journal of neural transmission. Supplementum.

[3]  J. Knoll.  The striatal dopamine dependency of life span in male rats. Longevity study with (−)deprenyl , 1988, Mechanisms of Ageing and Development.

[4]  B. Testa,et al.  Analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as monoamine oxidase substrates: a second ring is not necessary , 1987, Neuroscience Letters.

[5]  S. Banni,et al.  MPTP fails to induce lipid peroxidation in vivo. , 1987, Biochemical pharmacology.

[6]  K. Tipton,et al.  Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1986, The Biochemical journal.

[7]  G. Reynolds,et al.  Deprenyl is metabolized to methamphetamine and amphetamine in man. , 1978, British journal of clinical pharmacology.

[8]  C. Marsden,et al.  Increased caudate dopamine turnover may contribute to the recovery of motor function in marmosets treated with the dopaminergic neurotoxin MPTP , 1989, Neuroscience Letters.

[9]  J. LaManna,et al.  Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain. , 1989, The Journal of pharmacology and experimental therapeutics.

[10]  M. D’Incalci,et al.  Apoptosis Biochemical events and relevance to cancer chemotherapy , 1992, FEBS letters.

[11]  Z. Rossetti,et al.  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and free radicals in vitro. , 1988, Biochemical pharmacology.

[12]  S. Ohta,et al.  TETRAHYDROISOQUINOLINE AND 1-METHYL-TETRAHYDROISOQUINOLINE ARE PRESENT IN THE HUMAN BRAIN: RELATION TO PARKINSON’S DISEASE , 1987 .

[13]  R. Ramsay,et al.  Enhancement by tetraphenylboron of the interaction of the 1-methyl-4-phenylpyridinium ion (MPP+) with mitochondria. , 1989, Biochemical and biophysical research communications.

[14]  W. Nicklas,et al.  Studies on the Neurotoxicity of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine: Inhibition of NAD‐Linked Substrate Oxidation by Its Metabolite, 1‐Methyl‐4‐Phenylpyridinium , 1986, Journal of neurochemistry.

[15]  G. Painter,et al.  Accumulation of 1-methyl-4-phenylpyridinium (MPP+) into bovine chromaffin granules results in a large restriction of its molecular motion: a 13C and 31P NMR study. , 1988, Biochemical and Biophysical Research Communications - BBRC.

[16]  J. Sullivan,et al.  The interactions of monoamine oxidase with some derivatives of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1990, Journal of neural transmission. Supplementum.

[17]  O. H. Viveros,et al.  Subcellular compartmentalization of 1-methyl-4-phenylpyridinium with catecholamines in adrenal medullary chromaffin vesicles may explain the lack of toxicity to adrenal chromaffin cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[18]  K. Ohno,et al.  Increase of deleted mitochondrial DNA in the striatum in Parkinson's disease and senescence. , 1990, Biochemical and biophysical research communications.

[19]  K. Jellinger,et al.  Normal Mitochondrial Genome in Brain from Patients with Parkinson's Disease and Complex I Defect , 1990, Journal of neurochemistry.

[20]  Y. Agid,et al.  Iron and Aluminum Increase in the Substantia Nigra of Patients with Parkinson's Disease: An X‐Ray Microanalysis , 1991, Journal of neurochemistry.

[21]  R. Duvoisin,et al.  Dopaminergic toxicity of rotenone and the 1-methyl-4-phenylpyridinium ion after their stereotaxic administration to rats: Implication for the mechanism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity , 1985, Neuroscience Letters.

[22]  D. Murphy,et al.  Enhanced hydroxyl radical generation by 2′‐methyl analog of MPTP: Suppression by clorgyline and deprenyl , 1992, Synapse.

[23]  H. Rollema,et al.  Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP+ , 1989, Neuroscience Letters.

[24]  T. Nagatsu,et al.  An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions , 1988, Neuroscience Letters.

[25]  J. Langston,et al.  An electron microscopic study of MPTP-induced inclusion bodies in an old monkey , 1988, Brain Research.

[26]  R. Ramsay,et al.  Relation of superoxide generation and lipid peroxidation to the inhibition of NADH-Q oxidoreductase by rotenone, piericidin A, and MPP+. , 1992, Biochemical and biophysical research communications.

[27]  W. Tatton,et al.  Rescue of dying neurons: A new action for deprenyl in MPTP parkinsonism , 1991, Journal of neuroscience research.

[28]  M. Grumet.  Structure, expression, and function of, Ng‐CAM a member of the immunoglobulin superfamily involved in neuron‐neuron and neuron‐glia adhesion , 1992, Journal of neuroscience research.

[29]  M. da Prada,et al.  Evidence for the release of 1-methyl-4-phenylpyridinium (MPP+) from rat striatal neurons in vitro. , 1985, European journal of pharmacology.

[30]  C. Marsden,et al.  Further treatment with MPTP does not produce parkinsonism in marmosets showing behavioural recovery from motor deficits induced by an earlier exposure to the toxin , 1989, Neuropharmacology.

[31]  B. Halliwell.  Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke? , 1989, Acta neurologica Scandinavica. Supplementum.

[32]  P. Riederer,et al.  Is Parkinson's disease a progressive siderosis of substantia nigra resulting in iron and melanin induced neurodegeneration? , 1989, Acta neurologica Scandinavica. Supplementum.

[33]  J. Langston.  Mechanism of MPTP toxicity: more answers, more questions , 1985 .

[34]  W. Gibb,et al.  Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease. , 1991, Journal of neurology, neurosurgery, and psychiatry.

[35]  W. Koller,et al.  Posttraumatic movement disorders: A review , 1989, Movement disorders : official journal of the Movement Disorder Society.

[36]  E. Melamed,et al.  Immunity of Fetal Mice to Prenatal Administration of the Dopaminergic Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine , 1990, Journal of neurochemistry.

[37]  E. Neafsey,et al.  Inhibition of mitochondrial succinate oxidation--similarities and differences between N-methylated beta-carbolines and MPP+. , 1992, Archives of biochemistry and biophysics.

[38]  J. P. Schwartz,et al.  Accumulation of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Cultured Cerebellar Astrocytes , 1992, Journal of neurochemistry.

[39]  P. Riederer,et al.  IMPLICATIONS OF COMBINED TREATMENT WITH 'MADOPAR' AND L-DEPRENIL IN PARKINSON'S DISEASE A Long-term Study , 1977, The Lancet.

[40]  C. Marsden.  Parkinson's disease in twins. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[41]  S. Ohta,et al.  1‐Methyl‐ 1,2,3,4‐Tetrahydroisoquinoline, Decreasing in 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine‐Treated Mouse, Prevents Parkinsonism‐Like Behavior Abnormalities , 1991, Journal of neurochemistry.

[42]  W. Weiner,et al.  Could Parkinson's disease follow intra-uterine influenza? A speculative hypothesis. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[43]  R. Ramsay,et al.  Mechanism of the neurotoxicity of MPTP , 1990, FEBS letters.

[44]  R. M. Rose,et al.  Distinct monoamine oxidase A and B populations in primate brain. , 1985, Science.

[45]  J. Langston,et al.  The sensitivity of nigrostriatal dopamine neurons to MPP+ does not increase with age , 1988, Neuroscience Letters.

[46]  M. Swash,et al.  No viral antigens detected in brain tissue from a case of acute encephalitis lethargica and another case of post-encephalitic parkinsonism. , 1989, Journal of neurology, neurosurgery, and psychiatry.

[47]  Klaus P. Ebmeier,et al.  Does idiopathic parkinsonism in Aberdeen follow intrauterine influenza? , 1989, Journal of neurology, neurosurgery, and psychiatry.

[48]  T. Aiuchi,et al.  Enhancement by tetraphenylboron of inhibition of mitochondrial respiration induced by 1-methyl-4-phenylpyridinium ion (MPP+) , 1988, Neurochemistry International.

[49]  J. Cooper,et al.  Irreversible Inhibition of Mitochondrial Complex I by 1‐Methyl‐4‐Phenylpyridinium: Evidence for Free Radical Involvement , 1992, Journal of neurochemistry.

[50]  J. Parisi,et al.  Effects of l‐Methyl‐4‐Phenyl‐l,2,3,6‐Tetrahydropyridine in the Dog: Effect of Pargyline Pretreatment , 1989, Journal of neurochemistry.

[51]  J. Casida,et al.  Interaction of 1‐Methyl‐4‐Phenylpyridinium Ion (MPP+) and Its Analogs with the Rotenone/Piericidin Binding Site of NADH Dehydrogenase , 1991, Journal of neurochemistry.

[52]  R. Ramsay,et al.  The interaction of monoamine oxidases with tertiary amines. , 1991, Biochemical Society Transactions.

[53]  R. Ramsay,et al.  Biochemical mechanisms underlying MPTP-induced and idiopathic parkinsonism. New vistas. , 1993, Advances in neurology.

[54]  I. Mitchell,et al.  Sites of the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the macaque monkey include the ventral tegmental area and the locus coeruleus , 1985, Neuroscience Letters.

[55]  C. Marsden,et al.  Increased Nigral Iron Content and Alterations in Other Metal Ions Occurring in Brain in Parkinson's Disease , 1989, Journal of neurochemistry.

[56]  J. Langston,et al.  4-Phenylpyridine (4PP) and MPTP: the relationship between striatal MPP+ concentrations and neurotoxicity. , 1987, Life sciences.

[57]  J. Adams,et al.  Biochemical mechanisms of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity. Could oxidative stress be involved in the brain? , 1991, Biochemical pharmacology.

[58]  P. Sonsalla,et al.  Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[59]  C. Marsden,et al.  Basal Lipid Peroxidation in Substantia Nigra Is Increased in Parkinson's Disease , 1989, Journal of neurochemistry.

[60]  P. Löschmann,et al.  Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists , 1991, Nature.

[61]  R. Heikkila,et al.  Evaluation of the Biological Activity of Several Analogs of the Dopaminergic Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine , 1987, Journal of neurochemistry.

[62]  T. Baillie,et al.  Metabolism of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by liver homogenate fractions. , 1985, Journal of medicinal chemistry.

[63]  R. Ramsay,et al.  Oxidation of Analogs of l‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine by Monoamine Oxidases A and B and the Inhibition of Monoamine Oxidases by the Oxidation Products , 1989, Journal of neurochemistry.

[64]  R. Ramsay,et al.  Evidence that the inhibition sites of the neurotoxic amine 1-methyl-4-phenylpyridinium (MPP+) and of the respiratory chain inhibitor piericidin A are the same. , 1991, The Biochemical journal.

[65]  R. Ramsay,et al.  Structural dependence of the inhibition of mitochondrial respiration and of NADH oxidase by 1-methyl-4-phenylpyridinium (MPP+) analogs and their energized accumulation by mitochondria. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[66]  S. Ohta,et al.  Postmortem changes in mitochondrial respiratory enzymes in brain and a preliminary observation in Parkinson's disease , 1990, Journal of the Neurological Sciences.

[67]  J. Fuchs,et al.  Lifespan of immunosuppressed NMRI-mice is increased by deprenyl. , 1994, Journal of neural transmission. Supplementum.

[68]  K. Tipton,et al.  Uptake and accumulation of 1-methyl-4-phenylpyridinium by rat liver mitochondria measured using an ion-selective electrode. , 1992, The Biochemical journal.

[69]  S. Snyder,et al.  Neurology: Predicting Parkinson's disease , 1985, Nature.

[70]  D. Eisenberg,et al.  A cDNA that suppresses MPP+ toxicity encodes a vesicular amine transporter , 1992, Cell.

[71]  N. Castagnoli,et al.  Deuterium isotope effect measurements on the interactions of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidase B. , 1989, The Journal of biological chemistry.

[72]  J. Turrens,et al.  Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. , 1980, The Biochemical journal.

[73]  Bondy,et al.  Previously Published Works Uc Irvine Title: Effects of Mptp, Mpp+ and Paraquat on Mitochondrial Potential and Oxidative Stress , 2022 .

[74]  J. Cadet,et al.  Role of N-methyltransferases in the neurotoxicity associated with the metabolites of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and other 4-substituted pyridines present in the environment. , 1986, Biochemical pharmacology.

[75]  Y. Mizuno,et al.  Long-term effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine content in young and mature mice , 1987, Journal of the Neurological Sciences.

[76]  J. Vitorica,et al.  Impairment of glutamate uptake and absence of alterations in the energy-transducing ability of old rat brain mitochondria , 1985, Mechanisms of Ageing and Development.

[77]  R. Kalaria,et al.  On the mechanisms underlying 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity. II. Susceptibility among mammalian species correlates with the toxin's metabolic patterns in brain microvessels and liver. , 1988, The Journal of pharmacology and experimental therapeutics.

[78]  C. Marsden,et al.  Mitochondrial Complex I Deficiency in Parkinson's Disease , 1990, Lancet.

[79]  S. Snyder,et al.  Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[80]  L. A. Ordoñez,et al.  Behavioral alterations induced by formaldehyde-derived tetrahydroisoquinolines , 1981, Pharmacology Biochemistry and Behavior.

[81]  R. Clavier,et al.  Partial protection from the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by four different antioxidants in the mouse , 1985, Neuroscience Letters.

[82]  J. Sullivan,et al.  The neurotoxicity of MPTP and the relevance to Parkinson's disease. , 1990, Pharmacology & toxicology.

[83]  R. Ramsay,et al.  Mechanism-based inactivation of monoamine oxidases A and B by tetrahydropyridines and dihydropyridines. , 1990, The Biochemical journal.

[84]  C. Tanner,et al.  The role of environmental toxins in the etiology of Parkinson's disease , 1989, Trends in Neurosciences.

[85]  M. Naoi,et al.  Oxidation of N‐Methyl‐1,2,3,4‐Tetrahydroisoquinoline into the N‐Methyl‐Isoquinolinium Ion by Monoamine Oxidase , 1989, Journal of neurochemistry.

[86]  R. Ramsay,et al.  Biochemical Events in the Development of Parkinsonism Induced by 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine , 1987, Journal of neurochemistry.

[87]  T. Nagatsu.  MPTP and its relevance to parkinson's disease , 1987, Neurochemistry International.

[88]  S. Ohta,et al.  Confirmation of the enantiomers of 1-methyl-1,2,3,4-tetrahydroisoquinoline in the mouse brain and foods applying gas chromatography/mass spectrometry with negative ion chemical ionization. , 1990, Biomedical & environmental mass spectrometry.

[89]  C. Marsden,et al.  A redox reaction between MPP+ and MPDP+ to produce superoxide radicals does not impair mitochondrial function. , 1991, Biochemical pharmacology.

[90]  T. Buckman.  Toxicity of MPTP and structural analogs in clonal cell lines of neuronal origin expressing B type monoamine oxidase activity. , 1991, Molecular and chemical neuropathology.

[91]  Anthony E. Lang,et al.  Effect of deprenyl on the progression of disability in early Parkinson's disease. , 1989, The New England journal of medicine.

[92]  A. J. Bradbury,et al.  The toxic actions of MPTP and its metabolite MPP+ are not mimicked by analogues of MPTP lacking an N-methyl moiety , 1985, Neuroscience Letters.

[93]  M. Dudley.  The depletion of rat cortical norepinephrine and the inhibition of [3H]norepinephrine uptake by xylamine does not require monoamine oxidase activity. , 1988, Life sciences.

[94]  K. Jellinger,et al.  Mitochondrial DNA in Postmortem Brain from Patients with Parkinson's Disease , 1991, Journal of neurochemistry.

[95]  J. Parks,et al.  Abnormalities of the electron transport chain in idiopathic parkinson's disease , 1989, Annals of neurology.

[96]  D. T. Elmore.  Biochemical Mechanisms , 1963, Nature.

[97]  K. Tipton,et al.  The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (mptp) and its relevance to parkinson's disease , 1987, Neurochemistry International.

[98]  R. Kalaria,et al.  Correlation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity with blood-brain barrier monoamine oxidase activity. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[99]  B. Osuntokun,et al.  Comparison of the prevalence of Parkinson's disease in black populations in the rural United States and in rural Nigeria , 1988, Neurology.

[100]  C. Marsden,et al.  Anatomic and Disease Specificity of NADH CoQ1 Reductase (Complex I) Deficiency in Parkinson's Disease , 1990, Journal of neurochemistry.

[101]  T. Singer,et al.  Reversible inhibition and mechanism-based irreversible inactivation of monoamine oxidases by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1985, Biochemical and biophysical research communications.

[102]  T. Sick,et al.  Mechanisms of MPP+ Neurotoxicity: Oxyradical and Mitochondrial Inhibition Hypotheses , 1988 .

[103]  J. D. de Vries,et al.  Synthesis and toxicity toward nigrostriatal dopamine neurons of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analogues. , 1986, Journal of medicinal chemistry.

[104]  A. Graybiel,et al.  Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease , 1988, Nature.

[105]  M. Marmot,et al.  Could Parkinson's disease follow intra-uterine influenza?: a speculative hypothesis. , 1988, Journal of neurology, neurosurgery, and psychiatry.

[106]  N. Castagnoli,et al.  Interactions of the neurotoxic amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine with monoamine oxidases. , 1986, The Biochemical journal.

[107]  L. Sayre.  Biochemical mechanism of action of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). , 1989, Toxicology letters.

[108]  S. Snyder,et al.  Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin. , 1986, Science.

[109]  J. Langston,et al.  The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. , 1989, Science.

[110]  B. Ackrell,et al.  Is complex II involved in the inhibition of mitochondrial respiration by N-methyl-4-phenylpyridinium cation (MMP+) and N-methyl-beta-carbolines? , 1993, Biochemical Journal.

[111]  S. Ohta,et al.  Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline as novel endogenous amines in rat brain. , 1986, Biochemical and biophysical research communications.

[112]  Y. Kagawa,et al.  Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. , 1989, Biochemical and biophysical research communications.

[113]  S. Markey,et al.  Metabolism of [14C]MPTP in mouse and monkey implicates MPP+, and not bound metabolites, as the operative neurotoxin. , 1988, Chemical research in toxicology.

[114]  D. Murphy,et al.  Suppression of hydroxyl radical formation by MAO inhibitors: a novel possible neuroprotective mechanism in dopaminergic neurotoxicity. , 1994, Journal of neural transmission. Supplementum.

[115]  S. Markey,et al.  Differences in the metabolism of MPTP in the rodent and primate parallel differences in sensitivity to its neurotoxic effects. , 1985, Life sciences.

[116]  J. Langston,et al.  Older dopaminergic neurons do not recover from the effects of MPTP , 1987, Neuropharmacology.

[117]  Y. Mizuno,et al.  Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity and ATP synthesis by tetrahydroisoquinoline , 1988, Neuroscience Letters.

[118]  K. Takeshige,et al.  1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles. , 1990, Biochemical and biophysical research communications.

[119]  K. Lange.  Age-Dependent Effects of 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) in the Rat , 1990 .

[120]  G. Zeevalk,et al.  MK‐801 Fails to Protect Against the Dopaminergic Neuropathology Produced by Systemic 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine in Mice or Intranigral 1‐Methyl‐4‐Phenylpyridinium in Rats , 1992, Journal of neurochemistry.

[121]  J. Langston,et al.  Protection against DSP-4-induced neurotoxicity by deprenyl is not related to its inhibition of MAO B. , 1990, European journal of pharmacology.

[122]  Michael J. Adam,et al.  Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease , 1985, Nature.

[123]  S. Snyder,et al.  Predicting Parkinson's disease , 2018, Advances in Clinical Neuroscience & Rehabilitation.

[124]  P. Sonsalla,et al.  The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice. , 1986, European journal of pharmacology.

[125]  J. Gaál,et al.  Amphetamine-metabolites of deprenyl involved in protection against neurotoxicity induced by MPTP and 2'-methyl-MPTP. , 1994, Journal of neural transmission. Supplementum.

[126]  S. Ohta,et al.  A Novel and Neurotoxic Tetrahydroisoquinoline Derivative In Vivo: Formation of 1,3‐Dimethyl‐1,2,3,4‐Tetrahydroisoquinoline, a Condensation Product of Amphetamines, in Brains of Rats Under Chronic Ethanol Treatment , 1990, Journal of neurochemistry.

[127]  Duncan McGregor,et al.  Manganese neurotoxicity: a model for free radical mediated neurodegeneration? , 1982, Canadian journal of physiology and pharmacology.

[128]  Shirley Hansen,et al.  Exposure to cigarette smoke does not decrease the neurotoxicity of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice , 1987, Neuroscience Letters.

[129]  R. Uitti,et al.  Early Onset Parkinson's Disease in Saskatchewan - Environmental Considerations for Etiology , 1986, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[130]  W. Weiner,et al.  1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) selectively destroys dopaminergic neurons in cultures of dissociated rat mesencephalic neurons , 1986, Neuroscience Letters.

[131]  T. Aiuchi,et al.  Enhancement of the uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in mitochondria by tetraphenylboron. , 1992, Biochimica et biophysica acta.

[132]  R. Waring,et al.  Xenobiotic metabolism in Parkinson's disease , 1989, Neurology.

[133]  R. Fuller,et al.  Oral versus parenteral efficacy of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): differential effects on depletion of heart norepinephrine and of striatal dopamine in mice. , 1987, Biochemical pharmacology.

[134]  W. M. Davis,et al.  Metabolism of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse liver preparations. , 1984, Biochemical and biophysical research communications.

[135]  S. Snyder,et al.  MPTP: a neurotoxin relevant to the pathophysiology of Parkinson's disease. The 1985 George C. Cotzias lecture. , 1986, Neurology.

[136]  H. M. Geller,et al.  Potentiation by the Tetraphenylboron Anion of the Effects of 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine and Its Pyridinium Metabolite , 1990, Journal of neurochemistry.

[137]  C. Markham,et al.  Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Behavior, histology, and biochemistry , 1986, Experimental Neurology.

[138]  N. Satoh,et al.  Inhibition of rat brain monoamine oxidase by some analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylpyridinium ion , 1986, Neuroscience Letters.

[139]  R. Ramsay,et al.  Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria. , 1986, The Journal of biological chemistry.

[140]  J W Langston,et al.  Locus ceruleus lesions and eosinophilic inclusions in MPTP‐treated monkeys , 1986, Annals of neurology.