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Pyridine Derivatives: Structure-Activity Relationships Causing Parkinsonism-Like Symptoms

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Reviews of Environmental Contamination and Toxicology

Abstract

Ecological research frequently focuses on the harmful effects of environmental contaminants on the human nervous system. Many studies have been devoted to examining the neurotoxic effects of certain inorganic compounds (such as mercury and lead), trialkyltin, and low-molecular-weight organophosphate and organochlorine pesticides which induce nonspecific lesions of various regions of the nervous system, including the central nervous system (CNS) (Cremer 1981; Costa 1988; Kagan et al. 1988; Makhaieva et al. 1987, 1988).

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References

  • Agid Y, Blin S (1987) Nerve cell death in degenerative disease of the central nervous system: clinical aspects. In: Selective Neuronal Death. Wiley, Chichester (Ciba Foundation Symposium 126 ), pp 3–29.

    Google Scholar 

  • Ansher S, Cadet J, Jakoby W, Baker J (1986) Role of N-methyltransferases in the neurotoxicity associated with the metabolites of MPTP and other 4-substituted pyridines present in the environment. Biochem Pharmacol 35: 3359–3363.

    Article  PubMed  CAS  Google Scholar 

  • Arai Y, Hamamichi N, Kinemuchi H (1986) Time-dependent inhibition of rat brain MAO by analogue of MPTP, 4-(4-chlorophenyl)-l,2,3,6-tetrahydropyridine. Neurosci Lett 70: 255–260.

    Article  PubMed  CAS  Google Scholar 

  • Awasthi Y, Singh S, Rong-sen Shen, Abell C, Gessner W, Brossi A (1987) MPTP metabolites inhibit rat brain glutathione S-transferases. Neurosci Lett 81: 159–164.

    Article  PubMed  CAS  Google Scholar 

  • Bachurin S, Lermontova N, Solyakov L, Sablin S, Tkachenko S (1988a) Different neurochemical mode of action of pyridinium herbicides. Neurochem Intern 13, Suppl. 1: 85.

    Google Scholar 

  • Bachurin S, Sablin S, Dubova L (1988b) Monoamine oxidase (MAO) catalysis of dehydrogenation reaction of physiologically active aryltetrahydropyridines (THP). Abstracts 14th International Congress of Biochemistry, Prague, 1Y: 118.

    Google Scholar 

  • Bachurin S, Solyakov L, Tkachenko S, Lermontova N, Petrova L, Serkova T (1988c) Biochemical criteria for development of parkinsonism under the influence of MPTP and its pyridine analogues as the method for solution of nontoxic pesticides among pyridine containing compounds. Abstracts Conference on Chemistry and Technology of Pyridine Containing Pesticides ( USSR ), Chernogolovka (Russ), pp 240–241.

    Google Scholar 

  • Bachurin S, Sablin S, Dubova L (1988d) The catalytic properties of monoamine oxidase in dehydrogenation of physiologically active aryltetrahydropyridines. Abstracts Conference on Enzyme Engineering ( USSR ), Vilnus (Russ) 1: 11.

    Google Scholar 

  • Bachurin S, Sablin S, Grishina G, Gaidarova E, Dubova L, Zubov N (1989a) Monoamine oxidase catalysis of bioconversion of physiologically active 1-methvl-4-aryl-l,2,3,6-tetrahydropyridines. Bioorganic Chimia (Russ) 15: 620–626.

    CAS  Google Scholar 

  • Bachurin S, Sablin S, Dubova L (1990) Monoamine oxidase (MAO) catalysis of bioconversion of l-methyl-4-aryl-l,2,3,6,-tetrahydropyridines to physiologically active metabolites. Biocatalysis 4: 63.

    Article  Google Scholar 

  • Bachurin S, Solyakov L, Lermontova N, Tkachenko S, Kalashnikov V, Serkova T, Petrova L (1989b) The role of dopamine-uptake system in the development of experimental parkinsonism induced by MPTP and its pyridine analogues. Dokl Academ Nauk USSR (Russ) 307: 740–743.

    CAS  Google Scholar 

  • Bachurin S, Lermontova N, Solyakov L, Petrova L, Serkova T, Tkachenko S (1989c) Estimation of neurotoxicity of pyridine containing pesticides as a possible ecotoxicological factor. Abstracts Intern. Symposium “Environmental Stress”, Tampere, p 47.

    Google Scholar 

  • Bachurin S, Lermontova N, Sablin S, Solyakov L (1989d) Molecular basis of selectivity of 4-aryltetrahydropyridine derivatives. Abstracts Intern Symposium “Molecular basis of action of bioactive substances of behavior”, Tallin (Russ) p 8.

    Google Scholar 

  • Baker R (1975) Tetrahydropyridine insect repellent. US Patent 3,865,944 (cl. 424-263; A 01 ).

    Google Scholar 

  • Barbeau A, Dallaire L, Buu N, Poirier J, Ruchinka E (1985) Comparative behavioral, biochemical and pigmentary effects of MPTP, MPP+ and paraquat in Rana pipiens. Life Sci 37: 1529–1538.

    Article  PubMed  CAS  Google Scholar 

  • Barbeau A, Roy M, Bernier G, Campanella G, Paris S (1987) Parkinson’s disease: prevalence and environmental aspects in rural areas. Can J Neurol Sci 14: 36–41.

    PubMed  CAS  Google Scholar 

  • Barbeau A, Roy M, Cloutier T, Plasse L, Paris S (1986) Environmental and genetic factors in the etiology of Parkinson’s disease. In: Yahr M, Bergmann K (eds) Advances in Neurology, 45, Raven Press, New York, pp 249–306.

    Google Scholar 

  • Baskakov Y (1978) New synthetic plant growth regulators and herbicides. J. Mendeleev Natl Chem Soc (Russ) 2: 149–159.

    Google Scholar 

  • Berlin Y, Kost N (1960) 3-Piperideines. Uspechi Chimii (Russ) 29: 220–233.

    CAS  Google Scholar 

  • Booth R, Trevor A, Singer T, Castagnoli N (1989) Studies on semirigid tricyclic analogues of the nigrostriatal toxin MPTP. J Med Chem 32: 473–477.

    Article  PubMed  CAS  Google Scholar 

  • Bradbury A, Costal B, Domeney A, Jenner P, Marsden C, Nalor R, Tan C (1985). The neurotoxic actions of MPTP in the rat are not confined to dopamine and the substantia nigra. Br J Pharm 86: 691.

    Google Scholar 

  • Bradbury A, Brossi A, Costall B, Domerey A, Gessner W, Naylor R (1986) Biochemical changes caused by the infusion into the substantia nigra of the rat of MPTP and related compounds which antagonize dihydro-pteridine reductase. Neuropharmacology 25: 583–586.

    Article  PubMed  CAS  Google Scholar 

  • Brossi A, Gessner W, Fritz R (1986) Interaction of monoamine oxidase B with analogues of MPTP derived from prodine-type analgetics. J Med Chem 29: 444–445.

    Article  PubMed  CAS  Google Scholar 

  • Burns B, Chiueh C, Markey S, Ebert M, Jacobowitz D, Kopin I (1983) A primary model of parkinsonism: selective destruction of dopaminergic, neurons in the pars compacta of the substantia nigra by MPTP. Proc Natl Acad Sci (USA) 80: 4546–4450.

    Article  CAS  Google Scholar 

  • Chiba K, Peterson L, Castagnoli K, Trevor A, Castagnoli N (1985) Studies on the molecular mechanism of bioactivation of the selective nigrostriatal toxin MPTP. Drug Metab Dispos 13: 342–347.

    PubMed  CAS  Google Scholar 

  • Chiba K, Trevor A, Castagnoli N (1986) Uptake of MPP + by mouse brain synaptosomes. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 575–579.

    Google Scholar 

  • Costa L (1988) Interaction of neurotoxicants with neurotransmitter systems. Toxicology 49: 359–366.

    Article  PubMed  CAS  Google Scholar 

  • Coutts R, Scott J (1971) The chemistry and pharmacology of some tetrahydropyridines including arecoline and its derivatives. Can J Pharm Sci 6: 78–95.

    CAS  Google Scholar 

  • Cremer J (1981) The neurotoxic effect of environmental chemicals. In: Davison A, Thompson R (eds) The Molecular Basis of Neuropathology. London, pp 234–264.

    Google Scholar 

  • Corsini G, Pintus S, Bocchetta A (1986) Primate-rodent [H-3]-MPTP binding differences, and biotransformation of MPTP to a reactive intermediate in vitro. J Neural Trans Suppl 22: 55–66.

    CAS  Google Scholar 

  • Crooks P, Godin C. Damani L (1988) Formation of quaternary amines by N-methylation of azaheterocycles with homogenous amine N-methyltransferases. Biochem Pharmacol 37: 1673 1677.

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  • D’Amato R. Benham D, Snyder S (1987) Characterization of the binding of N-methyl-4-phenylpyridine, the toxic metabolite of the parkinsonian neurotoxin MPTP to neuromelanin. J Neurochem 48: 653–658.

    Article  PubMed  Google Scholar 

  • Davis G, Williams A, Markey S, Ebert M, Caine E, Reichert C, Kopin I (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues. Psychiat Res 1: 249–254.

    Article  CAS  Google Scholar 

  • Denton T, Howard B (1987) A dopaminergic cell line variant resistant to the neurotoxin MPTP. J Neurochem 49: 622–630.

    Article  PubMed  CAS  Google Scholar 

  • Di Monte D, Sandy M, Ekstromand G, Smith M (1986) Comparative studies on the mechanisms of paraquat and l-methyl-4-phenylpyridine ( MPP +) cytotoxicity. Biochem Biophys Res Comm 137: 303–309.

    Article  PubMed  Google Scholar 

  • Ellis R (1976) 4-Imidozolylsulfonylimidazoles. U.S. Patent 3,932,444 (cl 260–309).

    Google Scholar 

  • Evans D, Mitch C, Thomas D, Zimmerman D, Robey R (1980) Application of methylated amines to alkaloid synthesis. An expedient approach to the synthesis of morphine-based analgesics. J Am Chem Soc 102: 5955–5956.

    Article  CAS  Google Scholar 

  • Evans D, Mitch C (1982) Studies directed towards the total synthesis of morphine alkaloids. Tetrahedron Lett 23: 285–288.

    Article  CAS  Google Scholar 

  • Ferles M, Pliml J (1970) 3-Piperidines (1,2,3,6-tetrahydropyridines). Adv Heterocycl Chem 12: 43–101

    Article  CAS  Google Scholar 

  • Fritz R, Abell C, Patel N, Gessner W, Brossi A (1985) Metabolism of the neurotoxin MPTP by human liver monoamine oxidase. FEBS Lett 186: 224–228.

    Article  PubMed  CAS  Google Scholar 

  • Fuller R, Hemrick-Luecke S (1985) Inhibition of types A and B monoamine oxidase by MPTP. J Pharmacol Exp Therap 232: 696–701.

    CAS  Google Scholar 

  • Fuller R, Hermrick-Luecke S (1986a) Persistent depletion of striatal dopamine in mice by m-hydroxy-MPTP. Res Comm Chem Pathol Pharmacol 53: 167–171.

    CAS  Google Scholar 

  • Fuller R, Robertson D, Hemrick-Luecke S (1986b) Persistent depletion of striatal dopamine in mice by l-methyl-4-(2-thienyl)-l,2,3,6-tetrahydropyridine ( MPTP ). Biochem Pharmacol 35: 143–144.

    Article  PubMed  CAS  Google Scholar 

  • Fuller R, Hemrick-Luecke S (1987) Persistent depletion of striatal dopamine and its metabolites in mice by TMMP. J Pharm Pharmacol 39: 667–669.

    Article  PubMed  CAS  Google Scholar 

  • Gessner W, Brossi A, Bembenek M, Fritz R, Abell C (1986a) Studies on the mechanism of MPTP oxidation by human liver monoamine oxidase B. FEBS Lett 199: 100 102.

    Google Scholar 

  • Gibb C, Willoughly J, Glover V, Sandler M, Testa B, Jenner P, Marsden C (1987) Analogues of MPTP as monoamine oxidase substrates: a second ring is not necessary. Neurosci Lett 76: 316–322.

    Article  PubMed  Google Scholar 

  • Glover V, Gibb C Sandler M (1986) The role of MAO in MPTP toxicity. J Neurol Trans Suppl 20: 65–76.

    CAS  Google Scholar 

  • Gray A, Platz P, Henderson T, Chang T, Takahashi K, Dretchen K (1988) Approaches to protection against nerve agent poisoning (naphthylvinyl) pyridine derivatives as potential antidotes. J Med Chem 31: 807–814.

    Article  PubMed  CAS  Google Scholar 

  • Gridunov I, Prostakov N, Rodionova V (1964) Effect of l,2,5-trimethyl-4-phenyl-3,4-dehydropiperidine on the plastification of natural resin. Izv Vish Uch Zav Chim Chim Techn 7: 867 868.

    Google Scholar 

  • Hackmark G, Klosa Y (1977) 4,4-Diphenylpiperidines. Ger Offen 2.166.997 (cl.C07D211/14).

    Google Scholar 

  • Heikkila R, Hess A, Duvoisin R (1984a) Dopaminergic neurotoxicity of MPTP in mice, Science 224: 1451 1453.

    Google Scholar 

  • Heikkila R, Manzino L, Cabbat F, Duvoisin R (1984b) Protection against the neurotoxicity of MPTP by monoamine oxidase inhibitors. Nature 311: 467–469.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R, Hess A, Duvoisin R (1985a) Dopaminergic neurotoxicity of MPTP in the mouse: Relationships between monoamine oxidase, MPTP metabolism and neurotoxicity. Life Sci 36: 231 236.

    Google Scholar 

  • Heikkila R, Manzino L, Cabbat F, Duvoisin R (1985b) Studies of the oxidation of dopamine neurotoxin MPTP by monoamine oxidase B. J Neurochem 45: 1049–1054.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R, Youngster S, Panek D, Giovanni A, Sonsalla P (1988a) Studies with the neurotoxicant MPTP and several of its analogs. Toxicology 49: 493–501.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R, Kindt M, Sonsalla P, Giovanni A, Youngster S, McKeown K, Singer T (1988b) Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of MPTP. Proc Natl Acad Sci (USA) 85: 6172–6176.

    Article  CAS  Google Scholar 

  • Heilmann S, Rasmussen I (1984) Heterocyclic polymers. In: Kataritzky A, Rees C (eds) Comprehensive Heterocyclic Chemistry. New York, Pergamon Press, V.l, pp 269–315.

    Chapter  Google Scholar 

  • Hirato Y, Sugimura H, Takei H, Nagatsu T (1986) The effects of pyridinium salts, structurally related compounds of l-methyl-4-phenylpyridinium ion ( MPP +), on tyrosine hydroxylation in rat striatal tissue slices. Brain Res 397: 341–344.

    Article  Google Scholar 

  • Houlihan W (1970) Herbicidal sulfamides Ger Offen DE 1964441 (cl 07de, A 01n ).

    Google Scholar 

  • Hofle G, Steglich W, Vorbruggen H (1978) 4-Dialkylaminopyridines as highly active acylation catalysts. Angew Chem Int Ed Engl 17: 569–583.

    Article  Google Scholar 

  • Javitch J, D’Amato R, Strittmater S, Snyder S (1985) Parkinsonism inducing neurotoxin, MPTP: Uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci (USA) 82: 2173–2177.

    Article  CAS  Google Scholar 

  • Jenner P, Marsden C. Costal B, Naylor J (1986) MPTP and MPP + induced neurotoxicity in rodents and the common marmosets as experimental models of investigating Parkinson’s disease. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 563 567.

    Google Scholar 

  • Johannessen J, Savitt J, Markey C (1987) The development of amine substituted analogues of MPTP as unique tools for study of MPTP toxicity and Parkinson’s disease. Life Sci 40: 697–704.

    Article  PubMed  CAS  Google Scholar 

  • Kagan Y (1988) Toxicological aspects of studies on new pesticides. J Mendeleev Natl Chem Soc (Russ) 33: 624 631.

    Google Scholar 

  • Kinemuchi H, Fowler C, Tipton K (1987) The neurotoxicity of MPTP and its relevance to Parkinson’s disease. Neurochem Intl 1 1: 359–373.

    Article  Google Scholar 

  • Kiuchi K, Hagiwara M, Hidaka H, Nagatsu T (1988) Effect of the 1-methyl-4-phenylpyridinium ion on phosphorylation of tyrosine hydroxylase in rat pheo-chromocytoma PC 12 h cells. Neurosci Lett 89: 209–215.

    Article  PubMed  CAS  Google Scholar 

  • Koller W (1986) Paraquat and Parkinson’s disease. Neurology 36: 1147

    PubMed  CAS  Google Scholar 

  • Kopin I, Burns S, Chiuch C, Markey S (1986) MPTP-induced parkinsonian syndromes in humans and animals. In: Fisher A, Hanin J, Lachman C (eds) Alzheimer’s and Parkinson’s diseases: strategies for research and development. Plenum Press, New York, pp 519–530.

    Google Scholar 

  • Kryzhanovsky G, Atadzhanov M, Voronina T, Nerobkova L, Zagorevsky V, Sharkova L (1988a) MPP + -Induced parkinsonian syndrome in rats: clinical and EEG changes. Bull Exp Biol Med (Russ) 2: 147–149.

    Google Scholar 

  • Kryzhanovsky G, Atadzhanov M, Zagorevsky V, Sharkova L, Voronina T, Nerobkova L (1988b) Parkinson’s syndrome in rats induced by the administration of the MPTP. Bull Exp Biol Med (Russ) 4: 337–340.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Langston J, Irwin I, Langston E, Forno L (1984a) Pargyline prevents MPTP-induced parkinsonism in primates. Science 225: 1480–1482.

    Article  PubMed  CAS  Google Scholar 

  • Langston J, Irwin I, Langston E, Forno L (1984b) The importance of the 4-5 double bond for nuerotoxicity in primates of the derivative MPTP. Neurosci Lett 50: 289–294.

    Article  PubMed  CAS  Google Scholar 

  • Lazdin’sh I, Avots A (1979) Catalytic methods of synthesis of pyridine bases. Chim Heterocycl Compounds J (Russ) 8: 1011–1026.

    Google Scholar 

  • Lermontova N, Solyakov L, Bachurin S, Tkachenko S, Serkova T, Petrova L, Kalashnikov V (1989) An estimation of MPTP and some pyridine derivatives capability to produce parkinsonism. Bull Exp Biol Med (Russ) 6: 699–701.

    Google Scholar 

  • Lermontova N, Solyakov L, Bachurin S, Serkova T, Petrova L, Draniy O, Tkachenko S, Kalashnikov V (1990) Clinical and biochemical parameters of parkinsonism induced by MPTP and its tolyl-and methoxyphenyl-derivatives in the mouse C57B1/6. Bull Exp Biol Med (Russ) 10: 397–399.

    Google Scholar 

  • Leung L, Ottoboni S, Oppenheimer N, Castagnoli N (1989) Characterization of a product derived from the l-methyl-4-phenyl-2,3-dihydropyridinium ion, a metabolite of the nigrostriatal toxin MPTP. J Org Chem 54: 1052–1055.

    Article  CAS  Google Scholar 

  • Lewin R (1985) Parkinson’s disease: an environmental cause? Science 229: 257–258.

    Article  PubMed  CAS  Google Scholar 

  • Lewin R (1987) Environmental hypothesis for brain disease strengthened by new data. Science 237: 483–484.

    Article  PubMed  CAS  Google Scholar 

  • Makhaeva G, Malygin V, Martynov I (1987) Organophosphorus pesticides delayed neurotoxicity. Agrochimia (Russ) 2: 103–124.

    Google Scholar 

  • Makhaeva G, Malygin V, Martynov I (1988) The biochemical mechanisms of organophosphorus pesticides toxicity. Pestycydy 3: 39.

    Google Scholar 

  • Makino Y, Ohata S, Tachikawa D, Hirobe M (1988) Presence of tetra-hydroisoquino-line and 1-methyl-tetrahydro-isoquinoline in foods: compounds related to Parkinson’s disease. Life Sci 43: 373–378.

    Article  PubMed  CAS  Google Scholar 

  • Marsden C, Sandler M (1986) The MPTP story: an introduction. J Neurol Trans Suppl 20: 13.

    Google Scholar 

  • Mayer R, Kindt M, Heikkila R (1986) Prevention of the nigrostriatal toxicity of MPTP by inhibitors of 3,4–dihydroxyphenylethylamine. J Neurochem 47: 1073–1079.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Melnikov N, Novikov E, Kchaskin B (1975) Chemistry and biological activity of dipyridils and their derivatives. Moscow, Chimia (Russ) p 104.

    Google Scholar 

  • Mizuno Y, Sone N, Saitoh T (1987) Effect of MPTP and MPP+ ion on activities of the enzymes in the electron transport system in mouse brain. J Neurochem, 48: 1787–1793.

    Article  PubMed  CAS  Google Scholar 

  • Naoi M, Matsuura S, Parvez H, Takahashi T, Hirata Y, Minami M, Nagatsu T (1989) Oxidation of N-methyl-l,2,3,4-tetrahydroisoquinoline into the N-methyl-isoquinolinium ion by monoamine oxidase. J Neurochem, 52: 653–655.

    Article  PubMed  CAS  Google Scholar 

  • Nicklas W, Vyas J, Heikkila R (1985) Inhibition of NADH-linked oxidation in brain mitochondria by MPP, a metabolite of neurotoxin MPTP. Life Sci 36: 2503–2508.

    Article  PubMed  CAS  Google Scholar 

  • Nicklas W, Youngster S, Kindt M, Heikkila R (1987) MPTP, MPP + and mitochondrial function. Life Sci. 40: 721–729.

    Article  PubMed  CAS  Google Scholar 

  • Oreland L, Goherics C (1986) Brain and brain monoamine oxidase in aging and dementia of Alzheimer’s type. Progress in Neuro-Psychopharm Biol Psychiatry 10: 533–540.

    Article  CAS  Google Scholar 

  • Perry T, Yong V, Jones K, Wall R, Clavier R, Foulks J, Wright J (1985) Effects of MPTP and its metabolite, MPP+ ion, on dopaminergic nigrostriatal neurons in the mouse. Neurosci Lett 58: 321–326.

    Article  PubMed  CAS  Google Scholar 

  • Perry T, Yong V, Wall R, Jones K (1986a) Paraquat and two endogenous analogues of the neurotoxic substance MPTP do not damage dopamineragic nigrostriatal neurons in the mouse. Neurosci Lett 69: 285–289.

    Article  PubMed  CAS  Google Scholar 

  • Perry T, Yong V, Jones K, Wright J (1986b) Manipulation of glutathion contents fails to alter dopaminergic nigrostriatal neurotoxicity of MPTP in the mouse. Neurosci Lett 70: 261–265.

    Article  PubMed  CAS  Google Scholar 

  • Peterson L, Caldera P, Trevor A, Chiba K, Castagnoli N (1985) Studies on the l-methyl-4-phenyl-2,3-dihydropyridinim species 2,3-MPDP +, the monoamine oxidase catalysed oxidation product of the nigrostriatal toxin MPTP. J Med Chem 28: 1432–1436.

    Article  PubMed  CAS  Google Scholar 

  • Pileblad E, Carlsson A (1985) Catecholamine-uptake inhibitors prevent the neurotoxicity of MPTP in mouse brain. Neuropharmacology 24: 689–692.

    Article  PubMed  CAS  Google Scholar 

  • Ramsay R, Dadgar J, Trevor A, Singer T (1986a) Energy-driven uptake of N-methyl-4-phenylpyridine by brain mitochondria mediates the neurotoxicity of MPTP. Life Sci 39: 581–588.

    Article  PubMed  CAS  Google Scholar 

  • Ramsay R, Salach J, Dadgar J, Singer T (1986b) Inhibition of mitochondrial NADH dehydrogenase by pyridine derivatives and its possible relation to experimental and idiopathic parkinsonism. Biochem Biophys Res Comm 135: 269–275.

    Article  PubMed  CAS  Google Scholar 

  • Ramsay R, Singer T (1986c) Energy-dependent uptake of MPP +, the neurotoxic metabolite of MPTP, by mitochondria. J Biol Chem 261: 7585–7587.

    PubMed  CAS  Google Scholar 

  • Ramsay R, Koerberg S, Singer T (1987) Stopped-flow studies on the mechanism of oxidation of MPTP by bovine monoamine oxidase B. Biochemistry 26: 3045–3050.

    Article  PubMed  CAS  Google Scholar 

  • Reinbold A (1986) Plant growth regulators with retardant properties. Agrochimia (Russ) 5: 116.

    Google Scholar 

  • Riachi N, Arora P, Sayre L, Harik S (1988) Potent neurotoxic fluorinated MPTP analogs as potential probes in models of Parkinson disease. J Neurochem 50: 1319–1321.

    Article  PubMed  CAS  Google Scholar 

  • Ricourte G, Langston J, Delanney L (1985) Dopamine uptake blockers protect against the dopamine depleting effect of MPTP in the mouse striatum. Neurosci Lett 59: 264.

    Google Scholar 

  • Ricourte G, Langston J, Delanney L, Irwin I, Peroutka S, Forno L (1987) Fate of nigrostriatal neurons in young mature mice given MPTP: a neurochemical and morphological reassessment. Brain Res 403: 43–51.

    Article  Google Scholar 

  • Rios C, Tapia R (1987) Changes in lipid peroxidation induced by MPTP and MPP + in mouse brain homogenates. Neurosci Lett 77: 321–326.

    Article  PubMed  CAS  Google Scholar 

  • Ross S (1987) Pharmacological and toxicological exploitation of amine transports. TIPS, 8: 22–231.

    Google Scholar 

  • Rosetti Z, Sotgiu A, Sharp D, Hadjiconstantinou M, Neff N (1988) MPTP and free radicals in vitro. Biochem Pharmacol 37: 4573–4574.

    Article  Google Scholar 

  • Russ H, Przuntek H, Henning I, Pindrur U (1986) The protective effect of budipine against the nigrostriatal degeneration caused by MPTP and the interaction at the MPTP receptor binding site. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 449–453.

    Google Scholar 

  • Salach J, Singer T, Castagnoli N, Trevor A (1984) Oxidation of the neurotoxic amine MPTP by monoamine oxidase A and B and suicide inactivation of the enzymes by MPTP. Biochem Biophys Res Comm 125: 831–835.

    Article  PubMed  CAS  Google Scholar 

  • Schwartzbeck R (1974) Cyperquat, l-methyl-4-phenylpyridinium chloride, for the control of nutsedge (Cyperus spp.). Proc 12th British Confer pp 851–856.

    Google Scholar 

  • Sershen H, Debber E, Lajtha A (1987) Effect of ascorbic acid on the synaptosomal uptake of [H-3] MPP +, [H-3] dopamine and [C-14] GABA. J Neurosci Res 17: 298–301.

    Article  PubMed  CAS  Google Scholar 

  • Seto Y, Shinohara T (1987) Inhibitory effect of paraquat and its related compounds on the acetylcholinesterase activities of human erythrocytes and electric eel (.Electrophorus electricus). Agric Biol Chem 51: 2131–2138.

    Article  CAS  Google Scholar 

  • Singer T, Salach J, Crabtree D (1985) Reversible inhibition and mechanism-based inactivation of monoamine oxidase by MPTP. Biochem Biophys Res Comm 127: 707–712.

    Article  PubMed  CAS  Google Scholar 

  • Singer T, Salach J, Castagnoli N, Trevor A (1986) Interactions of the neurotoxic amine MPTP with monoamine oxidase. Biochem J 135: 785–789.

    Google Scholar 

  • Singer T, Castagnoli N, Ramsay R, Trevor A (1987) Biochemical events in development of parkinsonism induced by MPTP. J Neurochem 49: 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Singh Y, Swanson E, Sokolowski E, Kutty P, Krishna G (1988) MPTP and MPTP analogs induced cell death in cultured rat hepatocytes involving the formation of pyridinium metabolites. Toxicol Appl Pharmacol 96: 347–359.

    Article  PubMed  CAS  Google Scholar 

  • Sinha B, Singh Y, Krishna G (1986) Formation of superoxide and hydroxyl radicals from l-methyl-4-phenylpyridinium ion (MPP +): reductive activation by NADPH cytochrome P-450 reductase. Biochem Biophys Res Comm 135: 583–588.

    Article  PubMed  CAS  Google Scholar 

  • Shen R, Abell C, Gessner W, Brossi A (1985) Serotonergic conversion of MPTP and dopaminergic accumulation of MPP +. FEBS Lett 189: 225–230.

    Article  PubMed  CAS  Google Scholar 

  • Shen R, Abell C, Gessner W, Brossi A (1986) Hypothalamus uptake of [3 H] MPTP and striatal uptake of [H-3] MPP + in rat brain synaptosomes. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxine Producing a Parkinsonian Syndrome. Academic Press, New York, pp 563–567.

    Google Scholar 

  • Shimanskaya M, Leitis L (1989) Pesticides based on pyridine derivatives. Chim Heterocycl Compounds J (Russ) 5: 579–587.

    Google Scholar 

  • Shinochara T, Seto Y (1986) In vitro inhibition of acetylcholinesterase by paraquat. Agric Biol Chem 50: 255–256.

    Article  Google Scholar 

  • Snyder S, D’Amato R (1985) Predicting Parkinson’s disease. Nature 317: 198–199.

    Article  PubMed  CAS  Google Scholar 

  • Snyder S, D’Amato R, Nue G, Javitch J (1986) Selective uptake of MPP + by dopamine neurons is required for MPTP toxicity: studies in brain synaptosomes and PC-12 cells. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 191–201.

    Google Scholar 

  • Spencer P, Nunn P, Hugon J, Ludloph A, Ross S, Roy D, Robertson R (1987) Guam amytrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science 237: 517–522.

    Article  PubMed  CAS  Google Scholar 

  • Summers L (1980) The Bipyridinium Herbicides. Academic Press, London, pp 1–423.

    Google Scholar 

  • Sundeen I, Frederic P (1979) 4-(2-Phenyl)-ethyl-N-alkenyl-(or alkynyl)-1,2,3,6-tetrahydropyridines and their salts with acids. Ger Offen 2.904.451 (c. CO7d 213/24).

    Google Scholar 

  • Sundstrom E, Stromberg I, Tsutsumi T, Olson L, Jonsson G (1987) Studies on the effect of MPTP on central catecholamine neurons in mice. Comparison with three other strains of mice. Brain Res 405: 26–38.

    Article  PubMed  CAS  Google Scholar 

  • Takamidoh H, Naoi M, Nagatsu T (1987) Inhibition of type A monoamine oxidase by l-methyl-4-phenylpyridine. Neurosci Lett 73: 293–297.

    Article  PubMed  CAS  Google Scholar 

  • Tanner C (1989) The role of environmental toxin in the etiology of Parkinson’s disease. TINS 12: 49–54.

    PubMed  CAS  Google Scholar 

  • Tilson H, Burns R, Freed C, Heikkila R, Fuller R (1986) Animal models of MPTP toxicity: a panel discussion. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 149–158.

    Google Scholar 

  • Tkachenko S, Kalashnikov V, Lermontova N, Solyakov L, Sablin S, Bachurin S (1988a) Comparative study of pyridinium herbicides neurotoxicity mechanisms. Pestycydy 3: 55.

    Google Scholar 

  • Tkachenko S, Kalashnikov V, Mashkova I, Bachurin S (1988b) Regioselective synthesis of 2-and 4-aryl (hetaryl) pyridines. Abstracts Conference on Chemistry and Technology of Pyridine Containing Pesticides ( USSR ), Chernogolovka (Russ) pp 131–132.

    Google Scholar 

  • Tkachenko S, Kalashnikov V, Kalashnikova I, Mukhin S, Lermontova N, Solyakov L, Sablin S, Bachurin S (1989) Regioselective synthesis of physiologically active 4-aryl-, 4-styrylpyridines and its hydrogenate derivatives. Abstracts Conferenace on Chemistry of Physiologically Active Substances ( USSR ), Chernogolovka (Russ) p 126.

    Google Scholar 

  • Tollenaere G, Moereels H, Raymaekers L (1979) Atlas of three dimensional structure of drugs. Elsevier North-Holland Biochemical Press, Amsterdam, New York, Oxford pp 61–84.

    Google Scholar 

  • Trevor A, Castagnoli N, Singer T (1988) The formation of reactive intermediates in the MAO-catalyzed oxidation of the nigrostriatal toxin MPTP. Toxicology 49: 513–519.

    Article  PubMed  CAS  Google Scholar 

  • Trevor A, Chiba K, Yu E, Caldera P, Castagnoli K, Castagnoli N, Peterson L, Salach J, Singer T (1986) Metabolism of MPTP in vitro: the intermediate role of 2-3-MPDP + and studies on its chemical and biochemical reactivity. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 161–172.

    Google Scholar 

  • Vartanyan P (1984) Synthesis and biological activity of noncondensed cyclic derivatives of piperidine. Chim Pharm J (Russ) 18: 1294–1309.

    CAS  Google Scholar 

  • Vein A, Golubev V, Berzinsh Y (1981) Parkinsonism. ( Russ ), Riga Zinatne pp 1–325.

    Google Scholar 

  • Venkov A, Lukanov L, Mollov N (1988) 2-Acyl-l,2,3,4-tetrahydroisoquinolines as plant growth regulators. Pestycydy 3: 57.

    Google Scholar 

  • Voloshin M, Lukhanina E, Kolomiets B, Burchinskaya L, Nosenko N, Kuznetzov N (1989) Inhibition and excitation processes in thalamus motor nuclei neurons of cat in norm and after the nigrostriatal dopaminergic system injury produced by MPTP. Neurophysiol (Russ) 21: 620–628.

    CAS  Google Scholar 

  • Wilkening D, Vernier V, Arthand L, Treasy G, Kenney J, Nickolson V, Clark R, Smith D, Boswel G (1986) A Parkinson-like neurologic deficit in primates is caused by a novel 4-substituted piperidine. Brain Res 368: 239–246.

    Article  PubMed  CAS  Google Scholar 

  • Yong V, Perry T, Krisman A (1986) Depletion of glutathion brainstem of mice caused by MPTP is prevented by antioxidant pretreatment. Neurosci Lett 63: 56–60

    Article  PubMed  CAS  Google Scholar 

  • Youngster S, Duvoisin R, Hess A (1986) l-Methyl-4-(2′-methyl-phenyl)-l,2,3,6-tetrahydropyridine is a more potent dopaminergic neurotoxin than MPTP in mice. Eur J Pharm 122: 283–287.

    Article  CAS  Google Scholar 

  • Youngster S, Heikkila R (1986) Structure-activity studies on the mechanism of MPTP-MPP + -induced neurotoxicity. In: Markey S, Castagnoli N, Trevor A, Kopin I (eds) MPTP: A Neurotoxin Producing a Parkinsonian Syndrome. Academic Press, New York, pp 503–508.

    Google Scholar 

  • Youngster S, Sonsalla P, Heikkila R (1987) Evaluation of the biological activity of several analogs of the dopaminergic neurotoxin MPTP. J Neurochem 48: 929–934.

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann D, Cantrell B, Reel J, Hemrick-Luecke S, Fuller R (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: 1517–1620.

    Article  Google Scholar 

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Bachurin, S.O., Tkachenko, S.E., Lermontova, N.N. (1991). Pyridine Derivatives: Structure-Activity Relationships Causing Parkinsonism-Like Symptoms. In: Ware, G.W. (eds) Reviews of Environmental Contamination and Toxicology. Reviews of Environmental Contamination and Toxicology, vol 122. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-3198-1_1

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