Memantine (Axura, Akatinol) in Fibromyalgia and Chronic Fatigue Syndrome


Memantine (Axura, Akatinol) is…

An NMDA receptor antagonist that is FDA approved to treat moderate to severe Alzheimers.  A derivative of amantadine, which has been used for over 20 years to treat Alzheimers, Memantine blocks glutamate from exciting the  NMDA receptors believed to contribute to central sensitization.  Memantine also may down-regulate 5-HT3 receptors that can contribute to pain sensitivity. Memantine also enhances dopamine activity.


Memantine targets NMDA receptors that contribute to pain

Located in the dorsal horn of the spinal cord, the NMDA receptors are found in prime territory to regulate pain symptoms.  Dorsal horn neurons receive and filter sensory information from the body and transmit it to the brain.  Over activation of these neurons contributes to hypersensitivity pain states (central sensitization).  This suggests that toning down the NMDA receptors on these neurons could turn down pain levels as well.

NMDA receptors affecting drugs are often used in anesthesia for animals and sometimes in humans.  Ketamine and dextromorphan are two other NMDA receptor antagonists.  (Methadone and tramadol can also antagonize NMDA receptors). Some NMDA receptor drugs are used recreationally to produce states of euphoria.

Long term use of some NMDA receptors has proved problematic; one hope has been that Memantine will be a better long term solution.

A relatively new drug Memantine is being researched in a wide variety of conditions including ADHD, neuropathic pain, anxiety, epilepsy, SLS, depression, multiple sclerosis, autism, migraine, amyotrophic lateral sclerosis and others.

Memantine reduced neuropathic pain and improved cognition in laboratory animals and reduced pro-inflammatory cytokine expression and neurological issues in multiple sclerosis animal models. Memantine improved cognition and speech fluency in a large Alzheimer’s study. Memantine reduced central nervous system methylmercury damage in laboratory animals.

Fibromyalgia and Chronic Fatigue Syndrome (ME/CFS) Studies

Studies indicating raised levels of  glutamate in the insula, hippocampus, basal ganglia, posterior cingulate cortex regions (the ‘pain matrix’) of the brains of FM patients have ignited interest in Memantine.  Memantine improved cognition,depression and global function and produced a non-significant trend toward reduced pain in a small (n=10), preliminary, uncontrolled trial.  A larger fibromyalgia memantine trial will be getting underway soon.

Memantine and Lyrica were hypothesized to have synergistic effects in fibromyalgia  but no trials have yet occurred.

Side Effects

According to Wikipedia, Memantine is general well tolerated. (However check out Wikipedia’s page on NMDA receptor antagonists). Spanish fibromyalgia researchers report “Memantine has shown a very low incidence of side effects in clinical trials on humans”.

Adverse drug reactions can include confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations and others. Overdoses of NMDA receptor antagonists can cause  hallucinations, paranoid delusions, confusion, difficulty concentrating, agitation, mood alterations, nightmares,catatonia,  anaesthesia, and learning and memory problems. Abusers of these drugs can have significant cognitive problems.

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