Glutathione prevents N-methyl-D-aspartate receptor-mediated neurotoxicity

N-methyl-D-aspartate(NMDA) antagonists afford possible therapeutic modalities for stroke, trauma, and various neurodegenerative conditions thought to be mediated by excessive stimulation of NMDA receptors in the brain. To date, however, no drug has been demonstrated to be a safe NMDA antagonist at a dosage necessary for neuroprotection. In the present study, we use an in-vitro preparation to show that glutathione is capable of attenuating neuronal damage mediated by NMDA receptor activation. Both oxidized and reduced glutathione are protective, and an extracellular mechanism of action on the NMDA receptor-channel complex is suggested.