Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizziness. Severe side effects may include blood clots, psychosis, and heart failure. It is believed to work by acting on NMDA receptors, working as pore blockers of these ion channels. Memantine was approved for medical use in the United States in 2003. It is available as a generic medication. In 2020, it was the 152nd most commonly prescribed medication in the United States, with more than 3million prescriptions. Medical use Alzheimer's disease and dementia Memantine is used to treat moderate-to-severe Alzheimer's disease, especially for people who are intolerant of or have a contraindication to AChE (acetylcholinesterase) inhibitors. One guideline recommends memantine or an AChE inhibitor be considered in people in the early-to-mid stage of dementia. Memantine has been associated with a modest improvement; with small positive effects on cognition, mood, behavior, and the ability to perform daily activities in moderate-to-severe Alzheimer's disease. There does not appear to be any benefit in mild disease. Memantine when added to donepezil in those with moderate-to-severe dementia resulted in "limited improvements" in a 2017 review. The UK National Institute of Clinical Excellence (NICE) issued guidance in 2018 recommending consideration of the combination of memantine with donepezil in those with moderate-to-severe dementia. Psychiatry Bipolar disorder Memantine has been investigated as a possible augmentation strategy for depression in bipolar disorder but meta-analytic evidence does not support its clinical utility. Autism Effects in autism are unclear. Adverse effects Memantine is, in general, well tolerated. Common adverse drug reactions (≥1% of people) include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. Less common adverse effects include vomiting, anxiety, hypertonia, cystitis, and increased libido. Like many other NMDA antagonists, memantine behaves as a dissociative anesthetic at supratherapeutic doses. Despite isolated reports, recreational use of memantine is rare due to the drug's long duration and limited availability. Also memantine seems to lack effects such as euphoria or hallucinations. Memantine appears to be generally well tolerated by children with autism spectrum disorder. Pharmacology Glutamate A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be involved in the etiology of Alzheimer's disease. Targeting the glutamatergic system, specifically NMDA receptors, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system. Memantine is a low-affinity voltage-dependent