Mestinon

Mestinon or pyridostigmine bromide (generic name) 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 gravis. Regonol, another brand name for the drug pyridostigmine, is given as an injection and used to restore movement to back muscles after surgery.

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 and there are no clinical trials of Mestinon in ME/CFS. Case reports from just 3 patients with chronic fatigue syndrome showed all three either significantly improved or were able to exercise again without experiencing post-exertional malaise (PEM).

POTS
A small study of postural orthostatic tachycardia syndrome (POTS) 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 POTS improved with Mestinon.

The Exercise Response to Pharmacologic Cholinergic Stimulation in Preload Failure
This small trial of Mestinon is currently being conducted by David Systrom in Boston, US, and involves patients with preload failure, ME, CFS, Fibromyalgia and Dyspnea. This trial compares the effects of a single dose of 60mg of pyridostigmine bromide (Mestinon) with a placebo drug, and aims to measure the effects on post-exertional malaise and dyspnea. This trial is based on the theory that small fiber neuropathy causes autonomic system dysfunction, resulting in breathlessness and post-exertional malaise. The trial is expected to finish in 2019.

Droxidopa / Pyridostigmine in Orthostatic Hypotension
A phase 2 randomized controlled trial involving 25 people taking both droxidopa and pyridostigmine. It is being conducted by Dr Phillip Low at the Mayo Clinic, in Rochester, Minnesota, US. Researchers state:
 * "The hypothesis is that pyridostigmine will improve the safety factor of ganglionic neural transmission, while Droxidopa will replete the postganglionic neuron of norepinephrine (NE). This combination should result in enhanced orthostatic release of NE."

A Study of Pyridostigmine in Postural Tachycardia Syndrome
A three-day trial involving 50 people with POTS is being conducted by Dr Phillip Low at the Mayo Clinic, in Rochester, Minnesota, US. This is a blinded randomized controlled trial, comparing pyridostigmine with a placebo; researchers state they "expect pyridostigmine to improve tachycardia and stabilize blood pressure.

Side effects
Mestinon side effects that are most common include gastrointestinal symptoms including abdominal cramps, diarrhea and bloating, a runny nose, muscle twitching. Bradycardia, an abnormally slow heart rate may also occur, especially as a result of interaction with specific drugs.

Gulf War Illness
Pyridostigmine was given to Gulf War personnel to protect them from nerve gas. Dr Robert Haley reportedly found that pyridostigmine is involved in two of the three syndromes of Gulf War Illness. He reported that the nerve gas sarin interacted with pyridostigmine; the pesticide DEET did the same. These interactions (as well as drug alone) caused brain damage to 175,000 US Gulf War personnel. Gulf War Illness, possible interactions with DEET, other pesticides or organic solvents are not mentioned in the patient information.

Multiple chemical sensitivity
A 1999 review published by the RAND corporation states that veterans experiencing Gulf War Syndrome had symptoms resembling those of patients with Multiple chemical sensitivity (MCS), who commonly reported being exposed to pyridostigmine bromide or other AChE-inhibiting agents, nerve agents, pesticides or organic solvents, however there is a lack of peer-reviewed research on this topic. Increased chemical sensitives are not referred to in the patient information leaflet.

Overdose risk
Overdose can cause a "cholinergic crisis", which can be very dangerous.

Interviews and presentations

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

Notable studies

 * 2003, Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports (Full text)

Learn more

 * David Systrom
 * Mestinon for ME - personal experience of the drug
 * A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Cort Johnson
 * Pyridostigmine - drugs.com
 * Pyridostigmine - UK medicines information
 * Pyridostigmine - patient information leaflet (UK)
 * Treatments for Myasthenia Gravis