Skip to main content
SpringerLink
Log in
Book cover

Drugs for the Treatment of Parkinson’s Disease pp 205–226Cite as

Pyridine Toxins

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 88))

Abstract

Just 4 years ago there were few if any hints of a connection between pyridines and Parkinson’s disease. Yet a current review, particularly one focusing on experimental models, would be flawed without a discussion of this newly discovered relationship. This striking turn of events has been precipitated almost entirely by the discovery of a single compound, l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine, or, as it is now widely know, MPTP. In this chapter, we will explore the relevance of this compound and other pyridines to Parkinson’s disease. As should become clear, investigations into the biologic effects of these “pyridine neurotoxins” have provided a surprising number of research avenues, ranging from the development of new animal models for the disease, to a serious reassessment of etiologic factors.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ambani LM, Van Woert MH, Murphy S (1975) Brain peroxidase and catalase in Parkinson disease. Arch Neurol 32: 114–118

    Article  PubMed  CAS  Google Scholar 

  • Arai Y, Kinemuchi H, Hamamichi N, Satoh N, Tadano T, Kisara K (1986) Inhibition of rat brain monoamine oxidase by some analogues of l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and l-methyl-4-phenylpyridinium ion. Neurosci Lett 66: 43–48

    Article  PubMed  CAS  Google Scholar 

  • Ballard PA, Tetrud JW, Langston JW (1985) Permanent human parkinsonism due to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP): seven cases. Neurology (NY) 35: 949–956

    CAS  Google Scholar 

  • Barbeau A, Roy M, Langston JW (1985) Neurological consequence of industrial exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Lancet 1: 747

    Article  PubMed  CAS  Google Scholar 

  • Barbeau A, Dallaire L, Buu NT, Veilleux F, Boyer H, DeLanney LE, Irwin I, Langston EB, Langston JW (1986 a) New amphibian models for the study of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Life Sci 36: 1125–1134

    Google Scholar 

  • Barbeau A, Poirier J, Dallaire L, Rucinska E, Buu NT, Donaldson J (1986b) Studies on MPTP, MPP+ and paraquat in frogs and in vitro. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, New York, p 85–103

    Google Scholar 

  • Barnes RA (1960) Properties and reactions of pyridine and its hydrogenated derivatives. In: Klingsbert E (ed) Pyridine and derivatives, part 1. InterScience, New York, p 1–97

    Google Scholar 

  • Baumann RJ, Jameson HD, McKean HE, Haack DG, Weisberg LM (1980) Cigarette smoking and Parkinson disease: 1. A comparison of cases with matched neighbors. Neurology (NY) 30: 839–843

    CAS  Google Scholar 

  • Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 321: 169–171

    Article  Google Scholar 

  • Benedetti MS, Keane PE (1980) Differential changes in monoamine oxidase A and B activity in the aging rat brain. J Neurochem 35: 1026–1032

    Article  PubMed  CAS  Google Scholar 

  • Blakemore WF (1980) Isoniazid. In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicology. Williams and Wilkins, Baltimore, pp 476–489

    Google Scholar 

  • Boyce S, Kelly E, Reavill C, Jenner P, Marsden CD (1984) Repeated administration of N-methyl-4-phenyl-l,2,5,6-tetrahydropyridine to rats is not toxic to striatal dopamine neurons. Biochem Pharmacol 33: 1747–1752

    Article  PubMed  CAS  Google Scholar 

  • Bradbury AJ, Brossi A, Costall B, Domeney AM, Gessner W, Naylor RJ (1986) Biochemical changes caused by the infusion into the substantia nigra of the rat of MPTP and related compounds which antagonise dihydropteridine reductase. Neuropharmacology 25 (6): 583–586

    Article  PubMed  CAS  Google Scholar 

  • Brody F, Ruby (1960) Synthetic and natural sources of the pyridine ring. In: Klingsbert E (ed) Pyridine and derivatives, part 1. InterScience, New York, p 99–589

    Google Scholar 

  • Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80: 4546–4550

    Article  PubMed  CAS  Google Scholar 

  • Carvey PM, Kao LC, Klawans HL (1986) Permanent postural effects of MPTP in the guinea pig. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, New York, p 407–411

    Google Scholar 

  • Chiba K, Trevor A, Castagnoli N Jr (1984) Metabolism of the neurotoxic tertiary amine, MPTP, by brain monoamine oxidase. Biochem Biophys Res Commun 120: 574–578

    Article  PubMed  CAS  Google Scholar 

  • Chiba K, Peterson LA, Castagnoli KP, Trevor AJ, Castagnoli N Jr (1985 a) Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Drug Metab Dispos 13: 342–347

    Google Scholar 

  • Chiba K, Trevor AJ, Castagnoli N Jr (1985b) Active uptake of MPP+, a metabolite of MPTP, by brain synaptosomes. Biochem Biophys Res Commun 128: 1229–1232

    Article  Google Scholar 

  • Chiueh CC, Markey SP, Burns RS, Johannessen JN, Jacobowitz DM, Kopin IJ (1984 a) Selective neurotoxic effects of N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in subhuman primates and man: a new animal model of Parkinson’s disease. Psychopharmacol Bull 20: 548–553

    Google Scholar 

  • Chiueh CC, Markey SP, Burns RS, Johannessen J, Pert A, Kopin IJ (1984b) Neurochemical and behavioral effects of systemic and intranigral administration of N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in the rat. Eur J Pharmacol 100: 189–194

    Article  PubMed  CAS  Google Scholar 

  • Cohen G, Pasik P, Cohen B, Leist A, Mytilineou C, Yahr MD (1985) Pargyline and deprenyl prevent the neurotoxicity of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol 106: 209–210

    Article  Google Scholar 

  • Cote LJ, Kremzner LT (1983) Biochemical changes in normal aging in human brain. In: Mayeux R, Rosen WG (eds) The dementias. Raven, New York, p 19–30

    Google Scholar 

  • D’Amato RJ, Lipman ZP, Snyder SH (1986) Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin. Science 231: 987–989

    Article  PubMed  Google Scholar 

  • D’Amato RJ, Alexander GM, Schwartzman RJ, Kitt CA, Price DL, Snyder SH (1987) Molecular mechanisms of MPTP-induced toxicity. II. Neuromelanin: a role in MPTP-induced neurotoxicity. Life Sci 40: 705–712

    Article  PubMed  Google Scholar 

  • DeLanney LE, Ricaurte GA, Irwin I, Forno LS, Langston JW (1986) Neurotoxicity of MPTP varies depending on the route of administration (abstract). Soc Neurosci 12: 90

    Google Scholar 

  • Finnegan KT, Irwin I, DeLanney LE, Ricaurte GA, Langston JW (1987) 1,2,3,6-Tetrahydro-l-methyl-4-(methylpyrrol-2-yl)pyridine: studies on the mechanism of action of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. J Pharmacol Exp Ther 242: 1144–1151

    Google Scholar 

  • Forno LS, DeLanney LE, Irwin I, Langston JW ( 1986 a) Neuropathology of MPTP-treated monkeys: comparison with the neuropathology of human idiopathic Parkinson’s disease. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, New York, p 119–140

    Google Scholar 

  • Forno LS, Langston JW, DeLanney LE, Irwin I, Ricaurte GA (1986 b) Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 20: 449–455

    Google Scholar 

  • Fries DS, de Vries J, Hazelhoff B, Horn AS (1986) Synthesis and toxicity toward nigrostriatal dopamine neurons of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) analogues. J Med Chem 29 (3): 424–427

    Article  PubMed  CAS  Google Scholar 

  • Fuller RW, Hemrick-Luecke SK (1985) Effects of amfonelic acid, α-methyltyrosine, RO 4-1284 and haloperidol pretreatment on the depletion of striatal dopamine by l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine in mice. Res Commun Chem Pathol Pharmacol 48: 17–25

    PubMed  CAS  Google Scholar 

  • Fuller RW, Hemrick-Luecke SK (1986)Persistent depletion of striatal dopamine in mice by M-hydroxy-MPTP. Res Commun Chem Pathol Pharmacol 53(2): 167–172

    Google Scholar 

  • Gupta M, Gupta BK, Thomas R, Bruemmer V, Sladek JR Jr, Felten DL (1986) Aged mice are more sensitive to l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine treatment than young adults. Neurosci Lett 70: 326–331

    Article  PubMed  CAS  Google Scholar 

  • Hallman H, Olson L, Jonsson G (1084) Neurotoxicity of the meperidine analogue N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine on brain catecholamine neurons in the mouse. Eur J Pharmacol 97: 133–136

    Article  Google Scholar 

  • Hallman H, Lange J, Olson L, Stromberg I, Jonsson J (1985) Neurochemical and histochemical characterization of neurotoxic effects of l-methyl-4-phenyl-l,2,3,6-tetra-hydropyridine on brain catecholamine neurons in the mouse. J Neurochem 44: 117–127

    Article  PubMed  CAS  Google Scholar 

  • Heckman RA, Best FW (1981) An investigation of the lipophilic bases of cigarette smoke condensate. Tobacco Int 33: 83–89

    Google Scholar 

  • Heikkila RE, Hess A, Duvoisin RC (1984 a) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-l,2,5,6-tetrahydropyridine in mice. Science 224: 1451–1453

    Google Scholar 

  • Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC (1984b) Protection against the dop-aminergic neurotoxicity of l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 311: 467–469

    Article  PubMed  CAS  Google Scholar 

  • Herken H, Lange K, Kolbe H (1969) Brain disorders induced by pharmacological blockade of the pentose phosphate pathway. Biochem Biophys Res Commun 36 (1): 93–100

    Article  PubMed  CAS  Google Scholar 

  • Huy PTB, Meulemans A, Wassef M, Manuel C, Sterkers O, Amiel C (1983) Gentamicin persistence in rat endolymph and perilymph after a two-day constant infusion. Antimicrob Agents Chemother 23: 344–346

    Google Scholar 

  • Irwin I (1986) The neurotoxin l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP):a key to Parkinson’s disease? Pharm Res 3: 7–11

    Article  CAS  Google Scholar 

  • Irwin I, Langston JW (1985) Selective accumulation of MPP+ in the substantia nigra: a key to neurotoxicity? Life Sci 36: 207–212

    Article  PubMed  CAS  Google Scholar 

  • Irwin I, Langston JW, DeLanney LE (1987) 4-Phenylpyridine (4PP) and MPTP: the relationship between striatal MPP+ concentrations and neurotoxicity. Life Sci 40(8):731–740

    Google Scholar 

  • Jacobowitz DM, Burns RS, Chiueh CC, Kopin IJ (1984) N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes destruction of the nigrostriatal but not the mesolimbic dopamine system in the monkey. Psychopharmacol Bull 20: 416–422

    PubMed  CAS  Google Scholar 

  • Jarvis MF, Wagner GC (1985) Neurochemical and functional consequences following l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine (MPTP) and methamphetamine. Life Sci 36: 249–254

    Article  PubMed  CAS  Google Scholar 

  • Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82: 2173–3177

    Article  PubMed  CAS  Google Scholar 

  • Jenner P, Nadia MJ, Rupniak SR, Kelly E, Kilpatrick G, Lees A, Marsden CD (1984) l-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine-induced parkinsonism in the common marmoset. Neurosci Lett 50: 85–90

    Google Scholar 

  • Johannessen JN, Savitt JM, Markey CJ, Bacon JP, Weisz A, Hanselman DS, Markey SP (1987) Molecular mechanisms of MPTP-induced toxicity. I. The development of amine substituted analogues of MPTP as unique tools for the study of MPTP toxicity and Parkinson’s disease. Life Sci 40: 697–704

    Article  PubMed  CAS  Google Scholar 

  • Kalaria RN, Mitchel MJ, Harik SI (1986) Blood-brain barrier monoamine oxidase: [3H] pargyline binding to cerebral microvessels (abstract). Soc Neurosci 11 (2): 1260

    Google Scholar 

  • Kessler II, Diamond EL (1971) Epidemiologic studies of Parkinson’s disease. III. A community-based survey. Am J Epidemiol 96: 242–254

    Google Scholar 

  • Langston JW (1985 a) MPTP and Parkinson’s disease. Trends Neurosci 80:79–83

    Google Scholar 

  • Langston JW (1985 b) Mechanism of MPTP toxicity: more answers, more questions. TIPS 6:375–378

    Google Scholar 

  • Langston JW, Ballard PA (1983) Parkinson’s disease in a chemist working with 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). N Engl J Med 309: 310

    PubMed  CAS  Google Scholar 

  • Langston JW, Ballard PA (1984) Parkinsonism induced by l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can J Neurol Sci 11: 160–165

    PubMed  CAS  Google Scholar 

  • Langston JW, Irwin I (1986) MPTP: current concepts and controversies. Clin Neuropharmacol 9: 485–507

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Ballard PA, Tetrud JW, Irwin I (1983) Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219: 979–980

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Forno LS, Rebert CS, Irwin I (1984 a) Selective nigral toxicity after systemic administration of l-methyl-4-phenyl-l,2,5,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res 292: 390–394

    Google Scholar 

  • Langston JW, Irwin I, Langston EB, Forno LS (1984b) l-Methyl-4-phenylpyridinium ion (MPP+): identification of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett 48: 87–92

    Google Scholar 

  • Langston JW, Irwin I, Langston EB, Forno LS (1984 c) Pargyline prevents MPTP-induced parkinsonism in primates. Science 225: 1480–1482

    Google Scholar 

  • Langston JW, Irwin I, Langston EB, Forno LS (1984d) The importance of the 4–5 double bond for neurotoxicity in primates of the pyridine derivative MPTP. Neurosci Lett 50: 289–294

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Irwin I, DeLanney LE (1987) The biotransformation of MPTP and disposition of MPP+: the effects of aging. Life Sci 40 (8): 749–754

    Article  PubMed  CAS  Google Scholar 

  • Langston JW, Irwin I, Ricaurte G (1987) Neurotoxins, parkinsonism and Parkinson’s disease. Pharmacol Ther 32: 19–49

    Article  PubMed  CAS  Google Scholar 

  • Lent CM (1986) MPTP depletes neuronal monoamines and impairs the behavior of the medicinal leech. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, New York, pp 105–118

    Google Scholar 

  • Lewin R (1986) Age factors loom in parkinsonian research. Science 234: 1200–1201

    Article  PubMed  CAS  Google Scholar 

  • Loos D, Halbhubner K, Kehr W, Herken H (1977) Action of dopamine agonists on Parkinson-like muscle rigidity induced by 6-aminonicotinamide. NeuroScience 4: 667–676

    Article  Google Scholar 

  • Lyden A, Bondesson U, Larsson BS, Lindquist NG (1983) Melanin affinity of 1-methyl-4-phenyl-l,2,5,6-tetrahydropyridine, an inducer of chronic parkinsonism in humans. Acta Pharmacol Toxicol (Copenh) 53 (5): 429–432

    Article  CAS  Google Scholar 

  • Mann DMA, Yates PO (1983) Possible role of neuromelanin in the pathogenesis of Parkinson’s disease. Mech Ageing Dev 21: 193–203

    Article  PubMed  CAS  Google Scholar 

  • Markey SP, Johannessen JN, Chiueh CC, Burns RS, Herkenham MA (1984) Intraneuronal generation of a pyridinium metabolite may cause drug-induced parkinsonism. Nature 311: 464–467

    Article  PubMed  CAS  Google Scholar 

  • Marsden CD (1961) Pigmentation in the nucleus substantiae nigrae of mammals. J Anat 95 (2): 256–261

    PubMed  CAS  Google Scholar 

  • Melamed E, Rosenthal J, Clobus M, Cohen O, Frucht Y, Uzzan A (1985 a) Mesolimbic dopaminergic neurons are not spared by MPTP neurotoxicity in mice. Eur J Pharmacol 114: 970–1000

    Google Scholar 

  • Melamed E, Rosenthal J, Cohen O, Globus M, Uzzan A (1985 b) Dopamine but not norepinephrine or serotonin uptake inhibitors protect mice against neurotoxicity of MPTP. Eur J Pharmacol 116: 179–181

    Google Scholar 

  • Mytilineou C, Cohen G (1985) l-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine destroys dopamine neurons from the neurotoxic effect of l-methyl-4-phenylpyridinium ion. J Neurochem 45: 1951–1953

    Google Scholar 

  • Nefzger MD, Quadfasel FA, Karl VC (1968) A retrospective study of smoking and Parkinson’s disease. Am J Epidemiol 88: 149–158

    PubMed  CAS  Google Scholar 

  • Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by l-methyl-4-phenylpyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Life Sci 36: 2503–2508

    Article  PubMed  CAS  Google Scholar 

  • Nicklas WJ, Youngster SK, Kindt MV, Heikkila RE (1987) MPTP, MPP+ and mitochondrial function. Life Sci 40: 721–729

    Article  PubMed  CAS  Google Scholar 

  • Parisi JE, Burns RS (1986) The neuropathology of MPTP-induced parkinsonism in man and experimental animals. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, New York, p 141–148

    Google Scholar 

  • Perry TL, Yong VW, Ito M, Jones K, Wall RA, Foulks JG, Wright JM, Kish SJ (1985) l-Methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) does not destroy nigrostriatal neurons in the scorbutic guinea pig. Life Sci 36: 1233–1238

    Google Scholar 

  • Ransom BR, Kunis DM, Irwin I, Langston JW (1987) Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci Lett 75: 323–328

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Langston JW, DeLanney LE, Irwin I, Brooks JD (1985) Dopamine up-take blockers protect against the dopamine depleting effect of l-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) in the mouse striatum. Neurosci Lett 59: 259–264

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Langston JW, DeLanney LE, Irwin I, Peroutka SJ, Forno LS (1986) Fate of nigrostriatal neurons in young mature mice given l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP): a neurochemical and morphological reassessment. Brain Res 376 (1): 117–124

    Article  PubMed  CAS  Google Scholar 

  • Ricaurte GA, Irwin I, Forno LS, DeLanney LE, Langston EB, Langston JW (1987) Aging and MPTP-induced degeneration of dopaminergic neurons in the substantia nigra. Brain Res 403: 43–51

    Article  PubMed  CAS  Google Scholar 

  • Robinson DS, Nies A, Davis JN, Bunney WE, Davis JM, Colburn RW, Bourne HR, Shaw DM, Coppen AJ (1972) Ageing, monoamines and monoamine-oxidase levels. Lancet 1: 290–291

    Article  PubMed  CAS  Google Scholar 

  • Sahenk Z, Mendell JR (1980) Zinc pyridinethione. In: Spencer PS, Schaumburg HH (eds) Experimental and clinical neurotoxicology. Williams and Wilkins, Baltimore, pp 578–592

    Google Scholar 

  • Sahgal A, Andrews JS, Biggins JA, Candy JM, Edwardson JA, Keith AB, Turner JD, Wright C (1984) N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) affects locomotor activity without producing a nigrostriatal lesion in the rat. Neurosci Lett 48: 179–184

    Article  PubMed  CAS  Google Scholar 

  • Sayre LM, Arora PK, Iacofano LA, Harik SI (1986) Comparative toxicity of MPTP, MPP+ and 3,3-dimethyl-MPDP+ to dopaminergic neurons of the rat substantia nigra. Eur J Pharmacol 124: 171–174

    Article  PubMed  CAS  Google Scholar 

  • Schneider JS, Markham CH (1986) Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat. Tyrosine hydroxylase immunohistochemistry. Brain Res 373: 258–267

    Article  PubMed  CAS  Google Scholar 

  • Schneider JS, Yuwiler A, Markham CH (1986) Production of a Parkinson-like syndrome in the cat with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP): behavior, histology, and biochemistry. Exp Neurol 91: 290–307

    Article  Google Scholar 

  • Snyder SH, D’Amato RJ (1986) MPTP: a neurotoxin relevant to the pathophysiology of Parkinson’s disease. Neurology (NY) 36: 250–258

    CAS  Google Scholar 

  • Steranka LR, Polite LN, Perry KW, Fuller RW (1983) Dopamine depletion in rat brain by MPTP (l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine). Res Commun Substances Abuse 4: 315–323

    CAS  Google Scholar 

  • Sundstrom E, Jonsson G (1985) Pharmacological interference with the neurotoxic action of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) on central catecholamine neurons in the mouse. Eur J Pharmacol 110: 293–299

    Article  PubMed  CAS  Google Scholar 

  • Tetrud JW, Langston JW, Redmond DE, Roth RH, Sladek JR, Angel RW (1986) MPTP-induced tremor in human and non-human primates. Neurology (NY) 36 (Suppl 1): 308

    Google Scholar 

  • Trevor AJ, Castagnoli N Jr, Caldera P, Ramsay RR, Singer TP (1987) Bioactivation of MPTP: reactive metabolites and possible biochemical sequelae. Life Sci 40: 713–719

    Article  PubMed  CAS  Google Scholar 

  • Uhl GR, Javitch JA, Snyder SH (1985) Normal MPTP binding in parkinsonian substantia nigra: evidence for extraneuronal toxin conversion in human brain. Lancet 2: 956–957

    Article  Google Scholar 

  • Ward CD, Duvoisin RC, Ince SE, Nutt JD, Eldridge R, Calne DB (1983) Parkinson’s disease in 65 pairs of twins and in a set of quadruplets. Neurology (NY) 33: 815–824

    CAS  Google Scholar 

  • Wilson JS, Wilson JA (1986) Intracellular recordings in the caudate nucleus of normal and MPTP treated dogs. In: Markey SP, Castagnoli N Jr, Trevor AJ, Kopin IJ (eds) MPTP: a neurotoxin producing a parkinsonian syndrome. Academic, Orlando, pp 695–699

    Google Scholar 

  • Youngster SK, Duvoisin RC, Hess A, Sonsalla PK, Kindt MV, Heikkila RE (1986) l-Methyl-4-phenyl-(2′-methylphenyl)-l,2,3,6-tetrahydropyridine [2′CH3MPTP] is a more potent dopamine neurotoxin than MPTP in mice. Eur J Pharmacol 122: 283–287

    Google Scholar 

  • Ziering A, Berger L, Heineman SD, Lee J (1947) Piperidine derivatives. Part III. 4-Ayrlpiperidines. J Org Chem 12: 894–903

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman DM, Cantrell BE, Reel JK, Hemrick-Luecke SK, Fuller RW (1986) Characterization of the neurotoxic potential of m-methoxy-MPTP and the use of its n-ethyl analogue as a means of avoiding exposure to a possible parkinsonism-causing agent. J Med Chem 29: 1517–1520.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. W. Langston
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Irwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Neurology, UBC Health Sciences Centre Hospital, 2211 Wesbrook Mall, Vancouver, British Columbia, Canada, V6T 1W5

    Donald B. Calne Professor D.M., F.R.C.P., F.R.C.P.C. (Head) (Head)

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Langston, J.W., Irwin, I. (1989). Pyridine Toxins. In: Calne, D.B. (eds) Drugs for the Treatment of Parkinson’s Disease. Handbook of Experimental Pharmacology, vol 88. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-73899-9_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-73899-9_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-73901-9

  • Online ISBN: 978-3-642-73899-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation