Cholinergic and GABAergic neurotoxicity of some alkylating agents.
A series of nitrogen mustard derivatives was tested for neurotoxic effects on cholinergic and GABAergic markers at three rat brain regions: hippocampus, striatum and cortex. All compounds were administered intracerebroventricularly, and the enzymatic activities were measured 7 days after treatment. The effects of synthesised nitrogen mustard derivatives with indole, quinoline and hemicholinium backbone structures were compared. Of these compounds, only the hemicholinium analogue showed some preferential neurotoxicity to cholinergic neurones, thus offering a basis for designing novel, more specific cholinergic neurotoxins.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000477:Alkylating Agents; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase