Glutamate is the major neurotransmitter of the mammalian brain. Stimulation of glutamate receptors, especially the subgroup of NMDA receptors, induces nitric oxide and arachidonic acid synthesis in neurons. These agents freely diffuse across membranes and thus can play roles of messengers in particular brain functions. The aim of our study was to identify these roles in in vitro and in vivo models from mouse and rat. Exaggerated stimulation of NMDA receptors leads to neurological disorders such as some types of epilepsy and neurodegenerative diseases. We show that superoxide ions, which probably result from metabolic degradation of arachidonic acid, would be responsible of the neurotoxic action of NMDA. On the other hand, we observed that nitric oxide inhibits NMDA receptors. This effect would protect animals against epileptic and neurodegenerative diseases mediated by over-stimulation of these receptors. This endogenous regulation may play important roles in the functioning of glutamatergic neurotransmission.