Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid

In vivo and in vitro studies

G. Bringmann, D. Feineis, R. God, S. Fähr, W. Wesemann, H. W. Clement, C. Grote, W. Kolasiewicz, K. H. Sontag, Christine Marcelle Heim, T. A. Sontag, H. Reichmann, B. Janetzky, W. D. Rausch, M. Abdel-Mohsen, E. Koutsilieri, M. E. Götz, W. Gsell, B. Zielke, P. Riederer

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Due to their structural analogy to the dopaminergic neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), β-carbolines are discussed as potential natural inducers of Parkinson's disease (PD). In this paper, we report that the highly chlorinated compound 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) causes neurodegeneration of the dopaminergic system as demonstrated by in vivo analysis of nigrostriatal dopamine metabolism and by behavioural activities of rats as well as by histochemical examination of mouse brain tissue cultures and brain slices of TaClo treated rats. Furthermore, TaClo exhibits a strong inhibition of complex I of the mitochondrial respiratory chain. Since tryptamine ('Ta') readily reacts with chloral hydrate ('Clo') to give 'TaClo' even under mild quasi-physiological conditions (buffered water, pH 7.4, 37°C), a spontaneous formation of this heterocycle in man has to be taken into consideration after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene ('tri'). Indeed, TaClo was demonstrated to originate in rats after administration of its putative precursors.

Original languageEnglish (US)
Pages (from-to)83-102
Number of pages20
JournalBiogenic Amines
Volume12
Issue number2
StatePublished - Jun 27 1996

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Carbolines
Alkaloids
Chloral Hydrate
Trichloroethylene
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Neurotoxins
Brain
Electron Transport
Parkinson Disease
Dopamine
Water
Pharmaceutical Preparations
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Pharmacology

Cite this

Bringmann, G. ; Feineis, D. ; God, R. ; Fähr, S. ; Wesemann, W. ; Clement, H. W. ; Grote, C. ; Kolasiewicz, W. ; Sontag, K. H. ; Heim, Christine Marcelle ; Sontag, T. A. ; Reichmann, H. ; Janetzky, B. ; Rausch, W. D. ; Abdel-Mohsen, M. ; Koutsilieri, E. ; Götz, M. E. ; Gsell, W. ; Zielke, B. ; Riederer, P. / Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid : In vivo and in vitro studies. In: Biogenic Amines. 1996 ; Vol. 12, No. 2. pp. 83-102.
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title = "Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid: In vivo and in vitro studies",
abstract = "Due to their structural analogy to the dopaminergic neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), β-carbolines are discussed as potential natural inducers of Parkinson's disease (PD). In this paper, we report that the highly chlorinated compound 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) causes neurodegeneration of the dopaminergic system as demonstrated by in vivo analysis of nigrostriatal dopamine metabolism and by behavioural activities of rats as well as by histochemical examination of mouse brain tissue cultures and brain slices of TaClo treated rats. Furthermore, TaClo exhibits a strong inhibition of complex I of the mitochondrial respiratory chain. Since tryptamine ('Ta') readily reacts with chloral hydrate ('Clo') to give 'TaClo' even under mild quasi-physiological conditions (buffered water, pH 7.4, 37°C), a spontaneous formation of this heterocycle in man has to be taken into consideration after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene ('tri'). Indeed, TaClo was demonstrated to originate in rats after administration of its putative precursors.",
author = "G. Bringmann and D. Feineis and R. God and S. F{\"a}hr and W. Wesemann and Clement, {H. W.} and C. Grote and W. Kolasiewicz and Sontag, {K. H.} and Heim, {Christine Marcelle} and Sontag, {T. A.} and H. Reichmann and B. Janetzky and Rausch, {W. D.} and M. Abdel-Mohsen and E. Koutsilieri and G{\"o}tz, {M. E.} and W. Gsell and B. Zielke and P. Riederer",
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Bringmann, G, Feineis, D, God, R, Fähr, S, Wesemann, W, Clement, HW, Grote, C, Kolasiewicz, W, Sontag, KH, Heim, CM, Sontag, TA, Reichmann, H, Janetzky, B, Rausch, WD, Abdel-Mohsen, M, Koutsilieri, E, Götz, ME, Gsell, W, Zielke, B & Riederer, P 1996, 'Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid: In vivo and in vitro studies', Biogenic Amines, vol. 12, no. 2, pp. 83-102.

Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid : In vivo and in vitro studies. / Bringmann, G.; Feineis, D.; God, R.; Fähr, S.; Wesemann, W.; Clement, H. W.; Grote, C.; Kolasiewicz, W.; Sontag, K. H.; Heim, Christine Marcelle; Sontag, T. A.; Reichmann, H.; Janetzky, B.; Rausch, W. D.; Abdel-Mohsen, M.; Koutsilieri, E.; Götz, M. E.; Gsell, W.; Zielke, B.; Riederer, P.

In: Biogenic Amines, Vol. 12, No. 2, 27.06.1996, p. 83-102.

Research output: Contribution to journalArticle

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T1 - Neurotoxic effects on the dopaminergic system induced by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline), a potential mammalian alkaloid

T2 - In vivo and in vitro studies

AU - Bringmann, G.

AU - Feineis, D.

AU - God, R.

AU - Fähr, S.

AU - Wesemann, W.

AU - Clement, H. W.

AU - Grote, C.

AU - Kolasiewicz, W.

AU - Sontag, K. H.

AU - Heim, Christine Marcelle

AU - Sontag, T. A.

AU - Reichmann, H.

AU - Janetzky, B.

AU - Rausch, W. D.

AU - Abdel-Mohsen, M.

AU - Koutsilieri, E.

AU - Götz, M. E.

AU - Gsell, W.

AU - Zielke, B.

AU - Riederer, P.

PY - 1996/6/27

Y1 - 1996/6/27

N2 - Due to their structural analogy to the dopaminergic neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), β-carbolines are discussed as potential natural inducers of Parkinson's disease (PD). In this paper, we report that the highly chlorinated compound 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) causes neurodegeneration of the dopaminergic system as demonstrated by in vivo analysis of nigrostriatal dopamine metabolism and by behavioural activities of rats as well as by histochemical examination of mouse brain tissue cultures and brain slices of TaClo treated rats. Furthermore, TaClo exhibits a strong inhibition of complex I of the mitochondrial respiratory chain. Since tryptamine ('Ta') readily reacts with chloral hydrate ('Clo') to give 'TaClo' even under mild quasi-physiological conditions (buffered water, pH 7.4, 37°C), a spontaneous formation of this heterocycle in man has to be taken into consideration after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene ('tri'). Indeed, TaClo was demonstrated to originate in rats after administration of its putative precursors.

AB - Due to their structural analogy to the dopaminergic neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), β-carbolines are discussed as potential natural inducers of Parkinson's disease (PD). In this paper, we report that the highly chlorinated compound 'TaClo' (1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline) causes neurodegeneration of the dopaminergic system as demonstrated by in vivo analysis of nigrostriatal dopamine metabolism and by behavioural activities of rats as well as by histochemical examination of mouse brain tissue cultures and brain slices of TaClo treated rats. Furthermore, TaClo exhibits a strong inhibition of complex I of the mitochondrial respiratory chain. Since tryptamine ('Ta') readily reacts with chloral hydrate ('Clo') to give 'TaClo' even under mild quasi-physiological conditions (buffered water, pH 7.4, 37°C), a spontaneous formation of this heterocycle in man has to be taken into consideration after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene ('tri'). Indeed, TaClo was demonstrated to originate in rats after administration of its putative precursors.

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