The Journal of pharmacology and experimental therapeutics
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The dose-limiting toxicity of the chemotherapeutic agent vincristine is peripheral neuropathy, for which there is no established therapy. The amino acid glutamate has been proposed as a neuroprotectant for vincristine, but a full preclinical evaluation of its efficacy, safety and mechanism of action has been hampered by a lack of suitable animal models. We report the development of a Dark Agouti rat model of sensorimotor peripheral neuropathy, to investigate the neurotoxicity of cytotoxic drugs. ⋯ Our findings suggest that glutamate is likely to be a safe and effective neuroprotectant for patients receiving vincristine, and it warrants further clinical evaluation. The mechanism of this selective neuroprotection by glutamate remains to be elucidated. Our rat model may be of use in determining whether glutamate offers protection from other neurotoxic drugs.