NMDA Receptor Antagonists and Alzheimer's

NMDA (short for N-methyl-D-aspartate) receptor antagonists are a class of drugs that may help treat Alzheimer's disease, which causes memory loss, brain damage, and, eventually, death. There's no cure for Alzheimer's, but some drugs may slow it down.

Brain Chemicals

Your brain has billions of nerve cells called neurons. They pass electrical and chemical signals back and forth to process information or tell other cells in the body what to do. The chemicals that carry those signals are called neurotransmitters. One of these is called glutamate.

When it's passed from one neuron to another, it attaches itself to the new cell by using what's known as an NMDA receptor. NMDA allows glutamate to connect to a cell like a boat tying up at a dock. When glutamate is "docked" at an NMDA receptor, it passes calcium into the cell, carrying the electrical or chemical signal that last step. This is important for learning and memory.

If you have Alzheimer's disease, your cells can make too much glutamate. When that happens, the nerve cells get too much calcium, and that can speed up damage to them. NMDA receptor antagonists make it harder for glutamate to "dock" -- but they still let important signals flow between cells. Scientists are studying how they can be used against Alzheimer's.

Alzheimer's Treatment

Most Alzheimer's drugs focus on another chemical messenger known as acetylcholine. They keep acetylcholine levels high to keep nerve cells firing and slow the progress of the disease. But doctors do use one NMDA receptor antagonist: memantine (Namenda XR). It's been approved in the U.S. and Europe as a treatment for Alzheimer's disease. It's typically used when a person has more advanced symptoms and has shown modest benefits in patients with moderate to severe Alzheimer’s disease.

Memantine blocks some NMDA receptors when they're too active. The combination of memantine and a cholinesterase inhibitor leads to modest improvements in cognition and global outcomes in patients with advanced disease. Using it along with medications that focus on acetylcholine might make a bigger difference than those drugs would by themselves. It doesn't work well for everyone. Dizziness, is the most common side effect. but patients may also experience headaches and constipation, and, in rare cases, confusion.

Because they play a role in how nerve cells talk to one another, memantine and other NMDA receptor antagonists are also being studied as treatments for diseases like Parkinson's or amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Scientists are still trying to figure out how to use these chemicals in a way that helps people fight those illnesses.

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Similar Drugs

You might recognize some other NMDA receptor antagonists. Dextromethorphan, for instance, is a common ingredient in cough syrup.

Others have become associated with drug abuse:

  • Ketamine is an anesthetic widely used in people and animals. It keeps you from feeling pain during surgery or other procedures that can hurt. It can make you feel disconnected from your body or make you see things that aren't there (hallucinate). It's sometimes known as a "club drug." In recent years, scientists have studied whether ketamine can be used to treat depression. Other researchers have looked at whether it can be used to help people with bipolar disorder or brain injuries or if PCP and ketamine could be used to treat schizophrenia.
  • Phencyclidine, or PCP, was created as a surgical anesthetic, but doctors stopped using it after they found that it had serious side effects, like hallucinations and paranoia. As a street drug, nicknamed "angel dust," it's often linked to violent behavior.
WebMD Medical Reference Reviewed by Lisa Bernstein, MD on August 1, 2018

Sources

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Chen, H. Journal of Neurochemistry, June 2006.

Deardorff, W. Expert Opinion on Pharmacotherapy. Published online, July 2016.

Esposito, Z. CNS Neuroscience and Therapeutics, April 2013.

Zarate, C. Harvard Review of Psychiatry, October 2010.

Olivares, D. Current Alzheimer Research, July 2012.

Kapur, S. Molecular Psychiatry, September 2002.

National Institute on Drug Abuse: "DrugFacts: Hallucinogens."

University of Maryland, Center for Substance Abuse Research: "Ketamine."

Cleveland Clinic: "Hallucinogens -- LSD, Peyote, Psilocybin and PCP."

News release, University of Cincinnati: "Ketamine Shows Promise as Therapy for Brain Trauma and Mood Disorders."

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