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Glutamate: The Primary Excitatory Neurotransmitter


Glutamate is the primary excitatory neurotransmitter of the mammalian central nervous system. It exerts very powerful stimulating effects on neuronal activity. Glutamate is synthesized in the brain’s neuron terminals from both glucose and glutamine that is supplied by glial cells. Like other neurotransmitters, it is stored in presynaptic vesicles until needed for release across a synapse.

Glutamate and the Central Nervous System (CNS)

The reason glutamate is the primary excitatory neurotransmitter of the CNS is because, when released, it increases the likelihood that the targeted postsynaptic neuron will fire an action potential, which will lead to more firing and communication throughout the nervous system.

NMDA Receptor

Not only does it increase neuronal activity, it is also thought to play a key role in learning and thus memory formation. The glutamate receptor NMDA has become a major focus of attention in recent years because of its involvement in learning through making neuronal connections in the brain stronger. The term used for this in neuroscience is called long-term potentiation.

In basic terms, when the NMDA receptor is activated by glutamate on a postsynaptic neuron, the next time that receptor is stimulated, it won’t need as much glutamate as before to fire an action potential down the postsynaptic neuron. The connection between the two neurons is now stronger and will fire more often because less glutamate is required. Thus, the formation of a memory occurs as the neuronal connection is remembered and will fire again more readily.

Excess Glutamatergic activity

Although glutamatergic neurotransmission via the NMDA receptor is important for learning and memory, excess firing can have unwanted side effects. Overly-excited NMDA receptors have been shown to have a pivotal role in:

  • Low mood
  • Urges and compulsions
  • Neurotoxic effects in the brain
  • Injury
  • Electrical signals in the brain
  • Memory
  • Oxygen levels
  • Anxiousness
  • Headaches
  • Psychosis
  • Blood sugar management (1) (3) (4)

Both NMDA and AMPA (another major receptor of glutamate) receptor antagonists (that block glutamate from binding to receptors) have been shown to be powerfully neuroprotective in animal models of stroke, demonstrating the damaging effects of high glutamate levels (2).

Glutamate and Neurotransmitter Testing

We can see how adequate glutamatergic activity can be important for neurotransmission, learning, and memory, yet we can also see how excess glutamatergic activity can be neurotoxic and damaging to neuronal health. Thus, it is important to measure an individual’s level of glutamate in order to see if it is imbalanced.

If the glutamate level is low, implementing l-glutamine supplementation can help restore it and potentially increase glutamatergic neurotransmission. If the level is high, implementing supplemental support for GABA can help lower it as GABA is a potent inhibitor of glutamate. Also, high glutamate can be caused by MSG and aspartame intake. If your glutamate level is high, you should avoid having these ingredients in your diet as they may further elevate your levels.


  1. Cooper JR, Bloom FE, Roth RH. The Biochemical Basis of Neuropharmacology. New York: Oxford University Press, 1996.
  1. Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology. Brian S. Meldrum. Journal of Nutrition. 2000;130:1007S-1015S
  1. Glutamatergic mechanisms in different disease states: overview and therapeutic implications- An introduction. Tzschentke TM, Grunenthal GmbH. Amino Acids 2002;23(1-3):147-52 40.
  1. Plasma levels of neuroexcitatory amino acids in patients with migraine or tension headache. Alam Z, et al. J Neurol Sci. 1998;156(1):102-6.


Clinical Contributor

Nathan Bridges

Clinical Support Manager at Sanesco International, Inc.

Nathan Bridges is the Clinical Support Manager at Sanesco. He holds a Bachelors of Science in Health and Wellness Promotion with a minor in Psychology. He keeps a healthy mind and body by trail running, playing chess, and regularly reviewing recent research.


Connie Shoemaker, ND

Connie Shoemaker, ND

“Educating Sanesco’s clients is the culmination of a life’s work.” Beginning when she left the hospital environment to manage a functional laboratory, Genova Diagnostics (formerly Great Smokies Laboratories) in 1987, Dr. Connie Shoemaker has continued to increase her knowledge of herbs and biochemistry as a journey of love. With her bachelor’s in science from Western Carolina University, she had worked in hospital laboratories for the first twelve years of her career. Then, personal health challenges led her to discover a new approach to her health and a determination to share it with others. In 1991, she began teaching and educating innovative practitioners in the U.S. and internationally as a manager of marketing, sales, and customer service.

The addition of her Doctor of Naturopathy degree to her existing knowledge base expanded her knowledge and her respect for a more natural approach to healing through balance. At Sanesco, she initially served to oversee technical development of products and services.

Now, she educates Sanesco’s clients on application of the CSM™ model for their specific patients and how to integrate the CSM™ model with other modalities they offer in their practice. In her personal life, Connie educates private clients on various health topics.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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