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

Abstract

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.

Alzheimer's Disease and Stroke: A Tangled Neurological Conundrum

“…Another drug, memantine, works by blocking the overstimulated NMDA receptors and preventing the neurotoxicity caused by the massive release of glutamate [ 56 ]. Few preclinical studies have shown that memantine decreases the volume of infarction in stroke patients and also improves neurological outcomes [ 56 ]. Thus it can be used as an adjunct and alternative agent to protect neuronal tissue, which has undergone ischemia [ 56 ].…”

“…Few preclinical studies have shown that memantine decreases the volume of infarction in stroke patients and also improves neurological outcomes [ 56 ]. Thus it can be used as an adjunct and alternative agent to protect neuronal tissue, which has undergone ischemia [ 56 ]. So in a way, it can provide a window to minimize the brain damage until reperfusion therapy for stroke can be initiated [ 56 ].…”

Diagnosis and differential diagnosis flow diagram of Chinese post‐stroke aphasia types and treatment of post‐stroke aphasia

“…Cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and physostigmine), 49 , 50 , 51 N ‐methyl‐D‐aspartate (NMDA) receptor antagonists (memantine), 50 , 51 nerve repair and brain‐stimulating medications, and nootropic medications, such as piracetam, butylphthalide, ergoline, nimodipine, citicoline, Ginkgo biloba, and some proprietary Chinese medicines.…”

“…Extracellular release of glutamate in large amounts causes excessive activation of NMDA receptors after acute cerebral ischemia. 50 , 61 , 62 , 63 , 64 , 65 This triggers the activity of pathological molecules and a cascade effect, leading to cell death. As a reversible NMDA receptor antagonist, memantine blocks the excessive activation of neurons by glutamate.…”

Role of Glutamatergic Excitotoxicity in Neuromyelitis Optica Spectrum Disorders

“…Memantine may confer neuroprotection through more potent inhibition of extrasynaptic NMDA receptors (Zhao et al, 2006; Léveillé et al, 2008; Okamoto et al, 2009; Milnerwood et al, 2010; Xia et al, 2010) without significantly affecting physiologic glutamatergic transmission. In addition, this drug has few undesirable drug interactions or adverse effects and is a well-tolerated medication for neurological disorders (Seyedsaadat and Kallmes, 2019). Several studies have investigated the effects of memantine on neurons, and the drug is known to increase the release of glial cell neurotrophic factors, contributing to neuronal survival (Wu et al, 2009).…”