Mestinon

Mestinon or Pyridostigmine is an acetylcholinesterase inhibitor used to treat myasthenia gravis and Sjögren's syndrome. It inhibits the acetylcholinesterase enzyme from breaking down acetylcholine, resulting in higher circulating levels of the neurotransmitter. It cannot cross the blood brain barrier, and so only works on the peripheral nervous system. Mestinon is already licensed for use in the neuromuscular disease Myasthenia graves.

ME/CFS
In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors. A 2016 Australian study found that ME/CFS patients had significantly greater numbers of single nucleotide polymorphisms associated with the gene encoding for M3 muscarinic acetylcholine receptors. While these findings suggests some ME patients could benefit from Mestinon, anecdotal patient reports of Mestinon are mixed. A work in progress study of exercise intolerance in preload failure found that Mestinon improved exercise tolerance, but the study has not yet been published. A clinical trial of just 3 patients with chronic fatigue syndrome showed all three either significantly improved or were able to exercise again without experiencing post-exertional malaise.

POTS
A small study of postural orthostatic tachycardia syndrome in children found that 24.39% of patients had acetylcholine receptor autoantibodies. A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies. A small randomized crossover design trial found that patients with postural orthostatic tachychardia improved with Mestinon.

Gulf War Illness
Pyridostigmine was given to Gulf War personnel to protect them from nerve gas. The nerve gas sarin interacted with pyridostigmine; the pesticide DEET did the same. These interactions (as well as pesticide alone) caused brain damage to 175,000 US Gulf War personnel. Pyridostigmine is involved in two of the three syndromes categorized by Dr. Robert Haley.

In 2003, New Scientist 's March 29th print edition reported on Dr. Robert Haley and his team's research of Gulf War Illness and their identifying three distinct syndromes in Gulf war veterans that involved brain damage.
 * Syndrome 1: Symptoms are impaired cognition, distractions, and insomnia from the exposure of pesticide with basal ganglia damage.


 * Syndrome 2: The symptoms are confusion, disorientation, ataxia, and vertigo due to exposure to sarin and pyridostigmine with damage to the brain stem and basal ganlia.


 * Syndrome 3: Symptoms are pain, tingling, and numbness from exposure to DEET and pyridostigmine with damage to the brain stem.

Interviews and presentations

 * 2018, Advancements in ME/CFS Research, David M. Systrom, MD; Brigham and Women's Hospital | ME/CFSAlert 98

Notable studies

 * Post-exertional malaise
 * Exercise

Learn more

 * David Systrom
 * Mestinon for ME
 * A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise
 * Wikipedia