Biochemical lesions of the nigrostriatal system by TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) and derivatives.
In vivo voltammetry with carbon fibre electrodes was used to study the effects of highly halogenated tetrahydro-beta-carbolines on the striatal dopamine (DA) metabolism of the rat. As representatives of chloral-derived heterocycles, "TaClo" (1-trichloro-1,2,3,4-tetrahydro-beta-carboline) and its N-methylated derivative. "N-methyl-TaClo", were investigated. After intranigral injection of 10 micrograms TaClo, the DA activity in the ipsilateral striatum was reduced compared with the intact side. Application of N-methyl-TaClo (10 micrograms) resulted in a nearly total reduction of the DOPAC signal. Furthermore, also "TaBro" (1-tribromomethyl-1,2,3,4-tetrahydro-beta-carboline), the bromal-derived analogue of TaClo, was tested. The impairment of the DA metabolism in rats achieved with 10 micrograms TaBro was found to be between that observed after application of TaClo and N-methyl-TaClo, respectively. The results demonstrate the toxic potential of chloral- and bromal-derived beta-carbolines towards dopaminergic neurons.
Grote
C
C
Department of Neurochemistry, Philipps University, Marburg/Lahn, Federal Republic of Germany.
Clement
H W
HW
Wesemann
W
W
Bringmann
G
G
Feineis
D
D
Riederer
P
P
Sontag
K H
KH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry; D007980:Levodopa / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012680:Sensitivity and Specificity; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D002243:Carbolines; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D007980:Levodopa; D004298:Dopamine