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.