Neurotoxicity of pyridoxine analogs is related to coenzyme structure.
In very high doses, pyridoxine is neurotoxic in humans and other animals. Using morphometry and a model system of dorsal root ganglion neurons in culture, we found that several analogs of pyridoxine were neurotoxic in vitro. Those that may be converted into active coenzymes--pyridoxal, pyridoxine, and pyridoxamine--were almost equal in toxicity. Pyridoxic acid, which is not active, was nontoxic. Pyridoxamine 5-phosphate, which cannot enter cells, also was nontoxic. Several hypotheses that link coenzyme function to toxic effect are described.
D000818:Animals; D001665:Binding Sites; D001711:Biotransformation; D002478:Cells, Cultured; D003067:Coenzymes / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D051381:Rats
D003067:Coenzymes; D011736:Pyridoxine