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Because NMDA-R hypofunction (for example in GABAergic interneurons) has presumed down-stream effects (dis-inhibition of pyramidal cells) with increased glutamatergic neurotransmission and possible neurotoxicity, low affinity NMDA-R antagonism has been an alternative approach (memantine, riluzole)

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Understanding this fundamental distinction clarifies their complementary roles in oxidative stress management

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