The TaClo concept: 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo), a new toxin for dopaminergic neurons.
Due to its structural analogy to the neurotoxin MPTP, "TaClo" (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline), a compound readily originating in vitro from tryptamine ("Ta") and chloral ("Clo"), is discussed as a potential natural inducer of parkinsonian-like symptoms. Its spontaneous formation in man has to be taken into account after application of the drug chloral hydrate or after exposure to the solvent trichloroethylene. This first representative of chloral-derived heterocycles could now indeed be demonstrated to be formed in vivo after application of its putative precursors to rats. In vivo analysis of the nigrostriatal dopamine metabolism, behavioural studies, and histochemical findings as well as a strong inhibition of the complex I of the mitochondrial respiratory chain revealed the neurotoxic potential of TaClo on the dopaminergic system.
Bringmann
G
G
Institute of Organic Chemistry, University of Würzburg, Federal Republic of Germany.
God
R
R
Feineis
D
D
Wesemann
W
W
Riederer
P
P
Rausch
W D
WD
Reichmann
H
H
Sontag
K H
KH
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism / Q000633:toxicity*; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007274:Injections, Intraperitoneal; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D002243:Carbolines; D009498:Neurotoxins; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D004298:Dopamine