NMDA Receptors and How They're Involved in Disease

You may have heard of NMDA receptors while learning about a disease or medication, but do you understand what they are and why they are important?

First, it helps to understand what we mean by receptor. The brain contains cells called neurons. These are the cells that send and receive the electrical impulses that control your body.

Neurons are specialized—each one only deals with certain types of information. So, for example, one neuron may process information on pain and temperature but have nothing to do with visual perception or learning new information.

The chemicals that send information from neuron to neuron are called neurotransmitters. Some of the better-known ones include serotonin and dopamine. Neurotransmitters specialize in certain types of information, as well. For instance, serotonin is involved in the sleep cycle, while dopamine deals with movement and addiction.

For a neurotransmitter to move signals through a neuron, it first has to "unlock" it. That's where receptors come in. Think of receptors as boat slips or ports on your computer. Not every boat fits in every slip, and not every cable fits in every port. Neurotransmitters have keys that open the locks on a neuron's receptors, and that allows information to flow through your neurons.

What NMDA Receptors Do

NMDA stands for N-methyl-D-aspartate, which describes the chemical make-up of the receptors. NMDA receptors are involved in a lot of important processes in your brain. They're also believed to be involved in numerous illnesses involving the brain, and they're the targets of certain prescription drugs.

NMDA receptors are a critical part of what's called neuroplasticity, which basically means how malleable and adaptable our brains are—how able they are to learn new information, which means forming new pathways between neurons. In addition to learning new things, plasticity allows your brain to form new pathways when old ones are destroyed, such as by injury or disease.

As we age, our NMDA receptors naturally become less and less functional. Research suggests that this drop in activity is part of the age-related decline in plasticity, which causes memory impairment and a decreased ability to learn.

NMDA receptors are also one of a few receptors that process opiate/opioid painkillers in our brains.

NMDA Receptors and Neurotransmitters

NMDA receptors can be activated (unlocked) by binding with an assortment of neurotransmitters, including:

• Glutamate
• Aspartate
• Glycine
• D-serine

NMDA receptors work with these neurotransmitters to rev up activity in areas of your brain that help you learn new information and form memories. They stimulate and "excite" the neurons.

If the neurons stay in an excited state for too long, they can become overstimulated and start to function poorly. Eventually, they become so overexcited that they die.

That kind of overstimulation is called "excitotoxicity." Glutamate and aspartate, in excess, are both classified as excitotoxins. To keep excitotoxicity from killing our brain cells, we also have neurotransmitters that calm the neurons. They're called inhibitors.

Glycine, another one of the brain chemicals that bind with NMDA receptors, is an inhibitor in the spinal cord but is believed to be excitatory in the brain.

When our brains are healthy and functioning properly, excitatory and inhibitory neurotransmitters are generally able to keep things in balance so our neurons aren't in jeopardy of overstimulation. However, when things aren't working properly—i.e., a receptor is malfunctioning or neurotransmitter levels are out of balance—then we may start losing neurons to excitotoxicity.

Our bodies can't make new neurons, so when they die, we've lost irreplaceable parts of our brains. It's no surprise, then, that NMDA receptor problems are believed to be involved in a wide variety of central nervous system conditions, including many that are neurodegenerative.

Illnesses Linked to NMDA Receptor Malfunction

Neurodegenerative diseases believed to be linked to NMDA receptors malfunction include:

• Alzheimer's disease
• Amyotrophic lateral sclerosis (ALS)
• Huntington's disease
• Parkinson's disease
• Epilepsy

Other central nervous system conditions with suspected NMDA receptor involvement include:

• Fibromyalgia
• Chronic fatigue syndrome
• Migraine aura
• Some types of headache
• Anxiety
• Depression
• Schizophrenia
• Post-traumatic stress disorder
• Obsessive-compulsive disorder

Some conditions that don't involve NMDA receptor dysfunction may benefit from drugs that target NMDARs, such as:

• Phobia
• Stroke
• Pain from damaged nerves (neuropathy)

In phobias, NMDA receptor stimulating drugs are believed to help the amygdala (a part of the brain that deals with fear) re-learn new associations that help counter the fear.

In strokes, research suggests that inhibiting glutamate via NMDA receptors may help decrease damage to brain cells caused by lack of oxygen.

In neuropathic pain, these drugs may help boost the effect of painkillers due to their involvement with the opioid pathways.

Treatments Targeting NMDA Receptors

Brain chemistry is a tricky thing, and throwing it out of whack can be extremely dangerous. Even if it seems logical that something could help with your symptoms, it's crucial that you talk to a healthcare provider before trying anything that alters NMDA receptor function (or other aspects of how your brain works).

Many drugs and supplements are believed to alter the function of NMDA receptors. They come in two opposite forms: antagonists and agonists.

NMDA Receptor Antagonists

You're probably more familiar with the term "antagonist" when it refers to the villain of a story—the character who tries to slow down or block the hero from accomplishing his or her goals. In the medical sense, antagonists are drugs that slow or block things.

In the case of NMDA receptors, antagonists inhibit reception, meaning that they block neurotransmitters from unlocking these receptors. Many neurodegenerative diseases and other central nervous system disorders are sometimes treated with these types of medications.

Drugs that are classified as NMDA receptor antagonists include:

• Namenda (memantine)
• Ketamine
• Chloroform
• High doses of dextromethorphan (a cough suppressant in Mucinex, Robitussin, NyQuil and many other over-the-counter drugs)
• Strattera (atomoxetine)
• Symmetrel (amantadine)

Supplements in this category include:

• Agmatine
• Arginine
• Huperzine A
• Zinc

NMDA Receptor Agonists

An "agonist" is the opposite of an antagonist; it stimulates or increases activity. NMDA receptor agonists make it easier for neurotransmitters to access these receptors and increase the flow of information through the brain.

These drugs are sometimes used to treat mood and mental disorders, including schizophrenia and suicidal thoughts.

Some pharmaceutical NMDA receptor agonists are:

• Clozaril (clozapine)
• Seromycin (cycloserine)

Additionally, several experimental NMDA receptor agonists are undergoing clinical trials for depression.

Supplements that are NMDA receptor agonists include:

• Aspartic acid
• DHEA
• Theanine

A Word From Verywell

Knowing about NMDA receptors may help you gain a better understanding of your illness and possible treatments for it. Keep in mind that these receptors are part of an incredibly complex system—the human brain is one of the most complex systems that exist. Only a healthcare provider can properly diagnose and treat conditions that involve things like receptors and neurotransmitters.

It's common to think that supplements are "safe" treatments, but even natural substances can cause negative side effects and interact poorly with medications. Involve your healthcare provider and pharmacist in your treatment decisions to make sure you're not harming yourself as you try to get better.