Lesions in MS may be the result of oligodendroglial apoptosis and microglial activation rather than neuroinflammatory processes. Activated microglia secrete proinflammatory and neurotoxic factors (nitric oxide and peroxynitrites) that could cause neurodegeneration. In theory, inhibition of microglia would be protective in MS. Naltrexone, is capable of reducing microglial cytokine (IL-1β) and nitric oxide in glial cultures. If naltrexone is beneficial in MS, a possible mechanism of action is through reduction in microglial nitric oxide synthase activity resulting in decreased peroxynitrites production. Peroxynitrites are thought to inhibit glutamate transporters thereby increasing the synaptic concentrations of glutamate resulting in excitatory neurotoxicity.