Memantine for the treatment of ischemic stroke: Experimental benefits and clinical lack of studies

Stroke is an important cause of mortality and disability worldwide. Immediately after stroke onset, the ischemic cascade initiates and deleteriously affects neural cells. Time to reperfusion therapy is a critical determinant of functional recovery in stroke patients. Although recent trials have shown the significant efficacy of endovascular thrombectomy, either alone or with intravenous tissue plasminogen activator, in improving the functional outcomes of stroke patients with large vessel occlusion, hours can pass before patients receive reperfusion therapy. Moreover, many patients do not meet the eligibility criteria to receive reperfusion treatments. Therefore, an adjunct and alternative agent that can protect ischemic neuronal tissue during the hyperacute phase until reperfusion therapy can be administered may prevent further brain damage and enhance functional recovery. Memantine is a US Food and Drug Administration approved drug for the treatment of Alzheimer's disease. Memantine blocks overstimulated N-methyl-d-aspartate receptors and prevents neurotoxicity caused by massive glutamate release. Preclinical studies show that memantine decreases infarction volume and improves neurologic outcomes. However, few clinical studies have evaluated the safety and efficacy of memantine in stroke patients. This review article summarizes the current evidence for the role of memantine in the treatment of ischemic stroke and highlights areas for future research.