NEUROTOXIC EFFECTS ON THE DOPAMINERGIC SYSTEM INDUCED BY TACLO RICHLOROMETHYL-1,2,3,4-TETRAHYDRO-BETA-CARBOLINE), A POTENTIAL MAMMALIAN ALKALOID - IN-VIVO AND IN-VITRO STUDIES

Due to their structural analogy to the dopaminergic neurotoxin MPTP (N -methyl-4-phenyl-1,2,3,6-tetrahydropyridine), beta-carbolines are disc ussed as potential natural inducers of Parkinson's disease (PD). In th is paper, we report that the highly chlorinated compound ''TaClo'' tri chloromethyl-1,2,3,4-tetrahydro-beta-carboline) causes neurodegenerati on of the dopaminergic system as demonstrated by in vivo analysis of n igrostriatal dopamine metabolism and by behavioural activities of rats as well as by histochemical examination of mouse brain tissue culture s and brain slices of TaClo treated rats. Furthermore, TaClo exhibits a strong inhibition of complex I of the mitochondrial respiratory chai n. Since tryptamine ('Ta') readily reacts with chloral hydrate ('Clo') to give 'TaClo' even under mild quasi-physiological conditions (buffe red water, pH 7.4, 37 degrees C), a spontaneous formation of this hete rocycle in man has to be taken into consideration after application of the drug chloral hydrate or after exposure to the solvent trichloroet hylene ('tri'). Indeed, TaClo was demonstrated to originate in rats af ter administration of its putative precursors.