From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history
Mestinon box - pyridostigmine bromide

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.[1] Regonol, another brand name for the drug pyridostigmine, is given as an injection and used to restore movement to back muscles after surgery.[2]

ME/CFS[edit | edit source]

In 2015, a large German study found 29% of ME/CFS patients had elevated autoantibodies to M3 and M4 muscarinic acetylcholine receptors.[3][4] 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.[5] 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.[6] 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).[1]

POTS[edit | edit source]

A small study of postural orthostatic tachycardia syndrome (POTS) in children found that 24.39% of patients had acetylcholine receptor autoantibodies.[7] A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies.[8] A small randomized crossover design trial found that patients with POTS improved with Mestinon.[9]

Ongoing clinical trials[edit | edit source]

The Exercise Response to Pharmacologic Cholinergic Stimulation in Preload Failure[edit | edit source]

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.[10] 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.[10] This trial is based on the theory that small fiber neuropathy causes autonomic system dysfunction, resulting in breathlessness and post-exertional malaise.[10] The trial is expected to finish in 2019.

Droxidopa / Pyridostigmine in Orthostatic Hypotension[edit | edit source]

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." [11]

A Study of Pyridostigmine in Postural Tachycardia Syndrome[edit | edit source]

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.[12]

Side effects[edit | edit source]

Mestinon side effects that are most common include gastrointestinal symptoms including abdominal cramps, diarrhea and bloating, a runny nose, muscle twitching.[13] Bradycardia, an abnormally slow heart rate may also occur, especially as a result of interaction with specific drugs.[14][15][16]

Gulf War Illness[edit | edit source]

Pyridostigmine was given to Gulf War personnel to protect them from nerve gas.[17][18] Dr Robert Haley reportedly found that pyridostigmine is involved in two of the three syndromes of Gulf War Illness. He reported that the nerve gasSarin|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.[19][20][21][22] Gulf War Illness, possible interactions with DEET, other pesticides or organic solvents are not mentioned in the patient information.[14][15]

Multiple chemical sensitivity[edit | edit source]

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.[17] Increased chemical sensitives are not referred to in the patient information leaflet.[14][15]

Overdose risk[edit | edit source]

Overdose can cause a "cholinergic crisis", which can be very dangerous.[13][16]

Interviews and presentations[edit | edit source]

Notable studies[edit | edit source]

  • 2003, Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports[1] (Full text)

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 Kawamura, Yasuo; Kihara, Mikihiro; Nishimoto, Kazuhiro; Taki, Mayumi (May 2003). "Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports". Pathophysiology: The Official Journal of the International Society for Pathophysiology. 9 (3): 189–194. ISSN 0928-4680. PMID 14567934.
  2. "Regonol: Indications, Side Effects, Warnings". Retrieved April 14, 2019.
  3. Loebel, Madlen; Grabowski, Patricia; Heidecke, Harald; Bauer, Sandra; Hanitsch, Leif G.; Wittke, Kirsten; Meisel, Christian; Reinke, Petra; Volk, Hans-Dieter (February 2016). "Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome". Brain, Behavior, and Immunity. 52: 32–39. doi:10.1016/j.bbi.2015.09.013. ISSN 1090-2139. PMID 26399744.
  4. "Autoantibodies found in subset of CFS patients | #MEAction". The MEAction Network. Retrieved August 10, 2018.
  5. Johnson, Cort (June 17, 2016). "A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Health Rising". Health Rising. Retrieved August 26, 2018.
  6. Oliveira, R.K. (2016). "Pyridostigmine for Exercise Intolerance Treatment in Preload Failure". American Journal of Respiratory and Critical Care Medicine.
  7. Li, Jiawei; Zhang, Qingyou; Liao, Ying; Zhang, Chunyu; Hao, Hongjun; Du, Junbao (August 3, 2014). "The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome". Pediatric Cardiology. 36 (1): 165–170. doi:10.1007/s00246-014-0981-8. ISSN 0172-0643.
  8. Li, Hongliang; Yu, Xichun; Liles, Campbell; Khan, Muneer; Vanderlinde‐Wood, Megan; Galloway, Allison; Zillner, Caitlin; Benbrook, Alexandria; Reim, Sean (January 27, 2014). "Autoimmune Basis for Postural Tachycardia Syndrome". Journal of the American Heart Association. 3 (1). doi:10.1161/jaha.113.000755. ISSN 2047-9980. PMC 3959717. PMID 24572257.
  9. Raj, S.R. (May 31, 2005). "Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome". Circulation. 111 (21): 2734–2740. doi:10.1161/circulationaha.104.497594. ISSN 0009-7322.
  10. 10.0 10.1 10.2 Systrom, David. "The Exercise Response to Pharmacologic Cholinergic Stimulation in Preload Failure - NCT036745". Clinical trials. Retrieved April 15, 2019.
  11. "Droxidopa / Pyridostigmine in Orthostatic Hypotension -". Retrieved April 15, 2019.
  12. "A Study of Pyridostigmine in Postural Tachycardia Syndrome -". Retrieved April 15, 2019.
  13. 13.0 13.1 Myasthenia Gravis Hope Foundation (2017). "Treatments". Myasthenia Gravis Hope Foundation. Retrieved April 15, 2019.
  14. 14.0 14.1 14.2 Mylan (2018). "Mestinon patient info" (PDF). Electronic medicines compendium. Retrieved April 15, 2019.
  15. 15.0 15.1 15.2 "Mestinon Side Effects in Detail". Retrieved April 15, 2019.
  16. 16.0 16.1 "Mestinon 60mg Tablets - Summary of Product Characteristics (SmPC) - (eMC)". Electronic medicines compendium. Retrieved April 15, 2019.
  17. 17.0 17.1 Golomb, Beatrice A. (1999). "A Review of the Scientific Literature As It Pertains to Gulf War Illnesses". Volume 2: Pyridostigmine Bromide. Santa Monica, CA: RAND Corporation.
  18. Institute of Medicine (US) Committee on Health Effects Associated with Exposures During the Gulf War; Fulco, Carolyn E.; Liverman, Catharyn T.; Sox, Harold C. (2000). Pyridostigmine Bromide. National Academies Press (US).
  19. Haley, Robert (May 6, 2013). "Dr. Robert Haley, What Caused Gulf War Illness". YouTube. David Spencer.
  20. "Gulf war veterans have fertility problems". New Scientist. Retrieved August 26, 2018.
  21. Stencel, Christine; Burnette, Alison (April 9, 2010). "Gulf War Service Linked to Post-Traumatic Stress Disorder, Multisymptom Illness, Other Health Problems, But Causes Are Unclear". The National Academies of Sciences Engineering Medicine. Retrieved August 26, 2018.
  22. MacKenzie, Debora (November 3, 2004). "US in U-turn over Gulf war syndrome". New Scientist. Retrieved August 26, 2018.
  23. Systrom, David M. (July 2, 2018). "Advancements in ME/CFS Research, David M. Systrom, MD; Brigham and Women's Hospital". YouTube. ME/CFS Alert.