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Glutamate Regulators

Reviewed by: HU Medical Review Board | Last reviewed: February 2025 | Last updated: March 2025

Alzheimer’s disease is a neurodegenerative disease. This means that it is a disease that damages the cells of your brain (neurons) over time. When neurons are damaged, they cannot release chemicals called neurotransmitters. These chemicals send messages to other areas of the brain or body.1

Glutamate and brain signaling

Neurotransmitters can send “on” or “off” signals to other neurons. “On” signals make a neuron more likely to send its message to the next neuron in line. “Off” signals make a neuron less likely to send its message. Excitatory neurotransmitters send an “on” signal. Inhibitory neurotransmitters send an “off” signal.2

The excitatory neurotransmitter that the brain uses most is glutamate. Glutamate is very important for learning and memory. For the brain to work properly, the right amount of glutamate has to be released in the right area of the brain at the right time. In people living with Alzheimer’s disease, neurons release too much glutamate.2

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Glutamate and Alzheimer’s disease

In the early stages of Alzheimer’s disease, there is too much glutamate in the brain. The neurons respond more strongly to glutamate than they usually do. In the later stages of Alzheimer’s disease, there is not enough glutamate available in the brain. Both too much and too little glutamate affect the brain’s ability to make and store new memories.3

Regulating glutamate in Alzheimer’s disease

Drugs that modify how neurons respond to glutamate can improve the brain’s ability to think and create new memories. These drugs often work by preventing glutamate from sending certain “on” signals to neurons. The most well-known drug that regulates glutamate directly in the brain is Namenda® (memantine).4-8

This drug is approved by the US Food and Drug Administration (FDA) to treat moderate to severe Alzheimer’s disease. Its extended-release formula, Namenda XR, is also approved for Alzheimer’s.4-8

Namenda is usually used in combination with another type of drug called a cholinesterase inhibitor to make it more effective. An example of this combination is Namzaric® (memantine and donepezil).4,5,8

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. Common side effects of Memantine include:6-8

  • Headache
  • Dizziness
  • Diarrhea or constipation
  • Nausea or vomiting
  • Weight loss
  • Skin bruising

These are not all the possible side effects of Memantine. Talk to your doctor about what to expect when taking Memantine. You also should call your doctor if you have any changes that concern you when taking glutamate-regulating drugs.

Other things to know

Doctors may use many kinds of drugs to treat Alzheimer’s disease. Your doctor will work with you to choose which ones are best for you. You can also choose to participate in clinical trials for new drugs. These studies are important to find new treatments that may be more effective than what is currently available.5

Before beginning treatment for Alzheimer’s disease, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you take. This includes over-the-counter drugs.

Treatment results and side effects can vary from person to person. This treatment information is not meant to replace professional medical advice. Talk to your doctor about what to expect before starting and while taking any treatment.