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[60] Animal studies published in 1956 showed the therapeutic index of methotrexate was better than that of aminopterin, and clinical use of aminopterin was thus abandoned in favor of methotrexate

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Interestingly, low concentrations of NO generated by neuronal NOS or endothelial NOS have a physiological neuroprotective function and are involved in signaling pathway, while higher concentrations of NO synthesized by inducible NOS (iNOS) are neurotoxic (35, 36)