NMDA Receptor Antagonists and Alzheimer’s

Medically Reviewed by Dr. K on 22 March 2021

NMDA Receptor Antagonists and Alzheimer's

NMDA receptor antagonists (short for N-methyl-D-aspartate) are a class of medications that can assist in the treatment of Alzheimer's disease, which causes memory failure, brain injury, and ultimately death. Alzheimer's disease has no cure, although certain medications may help it progress more slowly.

Brain Chemicals

Neurons are billions of nerve cells that make up the brain. They transmit electrical and chemical signals to process information or instruct other cells in the body. Neurotransmitters are the molecules that carry these signals. Glutamate is one of these chemicals.

It binds itself to the new cell via an NMDA receptor as it is transmitted from one neuron to the next. NMDA helps glutamate to bind to a cell. As glutamate binds to an NMDA receptor, calcium is released into the cell, bringing the electrical or chemical signal to the final stage. This is important for memory and understanding.

Your cells will produce so much glutamate if you have Alzheimer's disease. As this occurs, the nerve cells absorb so much calcium, hastening their degeneration. While NMDA receptor antagonists make it more difficult for glutamate to “dock," they still enable essential signals to pass between cells. Scientists are studying how they can be used to combat Alzheimer's disease.

 

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.

Similar Drugs

Other NMDA receptor antagonists may be common to you. Cough syrup, for example, commonly contains dextromethorphan.

Others have become associated with drug addiction:

  • Ketamine is a commonly used anesthetic in both humans and animals. It stops you from suffering discomfort through surgery or other unpleasant procedures. It can make you feel out of touch with your body or lead you to see things that aren't really there (hallucinate). It's often referred to as a “party drug." Scientists have been researching whether ketamine should be used to relieve depression in recent years. Others also investigated whether it would benefit patients with bipolar illness or brain damage, as well as whether PCP and ketamine can be used to treat schizophrenia.
  • PCP (phencyclidine) was developed as a surgical anesthetic, but it was discontinued when doctors learned that it induced severe side effects such as hallucinations and paranoia. It's often associated with violent behavior. It is a  street drug known as “angel dust."

Sources

Referenced on 2.3.2021:

  1. Alzheimer's Association: “Current treatments."
  2. Strong, K. Expert Opinion on Therapeutic Patents, October 2014.
  3. Chen, H. Journal of Neurochemistry, June 2006.
  4. Deardorff, W. Expert Opinion on Pharmacotherapy. Published online, July 2016.
  5. Esposito, Z. CNS Neuroscience and Therapeutics, April 2013.
  6. Zarate, C. Harvard Review of Psychiatry, October 2010.
  7. Olivares, D. Current Alzheimer Research, July 2012.
  8. Kapur, S. Molecular Psychiatry, September 2002.
  9. National Institute on Drug Abuse: “DrugFacts: Hallucinogens."
  10. University of Maryland, Center for Substance Abuse Research: “Ketamine."
  11. Cleveland Clinic: “Hallucinogens — LSD, Peyote, Psilocybin and PCP."
  12. https://www.webmd.com/alzheimers/guide/nmda-receptor-antagonists

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