Ethylenebisdithiocarbamate enhances MPTP-induced striatal dopamine depletion in mice.
Diethyldithiocarbamate (DDC) has been shown to enhance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine depletion in mice. Surprisingly, although DDC is a prototypic member of a class of compounds called dithiocarbamates (DTCs) that are widely used in industry and agriculture, only one study has investigated the interaction of dithiocarbamates other than DDC with MPTP. The purpose of the present study was to investigate whether two other widely used dithiocarbamates, ethylenebisdithiocarbamate (EBDC) and methyldithiocarbamate (MDC), would also enhance MPTP toxicity. The dithiocarbamates were administered to mice intraperitoneally at various doses with or without MPTP. Doses were chosen based on the LD50 values for each compound. DDC was also tested (using a previously reported dose) for comparison. Striata were obtained one week later for dopamine measurements. Consistent with previous reports, DDC produced statistically significant enhancement in MPTP-induced striatal dopamine depletion. EBDC also produced significant exacerbation of MPTP-induced dopamine depletion. In contrast to DDC and EBDC, MDC failed to enhance the effects of MPTP, even when administered at doses of high lethality. Further studies of the dithiocarbamate class of compounds may help to elucidate the mechanism of DDC and EBDC enhancement of MPTP toxicity. Given the widespread use of these compounds in the environment such studies may also provide clues to the process of nigrostriatal cell degeneration in Parkinson's disease.
McGrew
D M
DM
The Parkinson's Institute, Sunnyvale, CA 94089, USA.
Irwin
I
I
Langston
J W
JW
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D004357:Drug Synergism; D005028:Ethylenebis(dithiocarbamates) / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000378:metabolism; D010575:Pesticides / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
D015259:Dopamine Agents; D005028:Ethylenebis(dithiocarbamates); D010575:Pesticides; D013859:Thiocarbamates; C008435:methyldithiocarbamate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine