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 language||English (US)|
|Number of pages||20|
|State||Published - Jun 27 1996|
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