NS-398 is a small molecule inhibitor of Cox (cyclooxygenase), relatively selective for Cox-2 (IC50 of 3.8 μM) over Cox-1 (IC50 of > 100 μM). The inflammatory response to injury and stimulus is associated with Cox-2 activity, and this activity is thought to be related to neurotoxicity presented in the progression of cerebral ischemia. NS-398 intervenes upon this progression through inhibition of Cox-2, potentially by suppressing the synthesis of Cox-2 reaction products such as prostanoids and superoxide radicals. Additionally, NS-398 is shown to reduce the extent of neuronal damage caused by glutamate excitotoxicity and by N-methyl-D-aspartate injection through blocking the Cox-2 response. Another report assessing Cox-2-mediated neuronal damage associated with methamphetamine further indicates that reactive oxygen species generated by Cox-2 are culprit in this process, rather than prostaglandin expression strongly associated with Cox enzymes and the inflammatory response.