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Mestinon
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[[File:Mestinon-package.jpg|250x250px|alt=Mestinon box - pyridostigmine bromide|thumb]] '''Mestinon''' or '''pyridostigmine bromide''' (generic name) is an [[Acetylcholinesterase|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|myasthenia gravis]].<ref name="Kawamura2003">{{Cite journal | last = Kawamura | first = Yasuo | author-link = | last2 = Kihara | first2 = Mikihiro | authorlink2 = | last3 = Nishimoto | first3 = Kazuhiro | authorlink3 = | last4 = Taki | first4 = Mayumi | authorlink4 = | authorlink5 = | date = May 2003 | title = Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports|url=http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.587.6854&rep=rep1&type=pdf|journal=Pathophysiology: The Official Journal of the International Society for Pathophysiology|volume=9|issue=3|pages=189–194|issn=0928-4680|pmid=14567934|quote=|via=}}</ref> '''Regonol''', another brand name for the drug pyridostigmine, is given as an injection and used to restore movement to back [[Muscle|muscles]] after surgery.<ref>{{Cite web|url=https://www.drugs.com/cdi/regonol.html | title = Regonol: Indications, Side Effects, Warnings|website=Drugs.com|language=en|access-date=2019-04-14}}</ref> ==ME/CFS== In 2015, a large [[Germany|German]] study found 29% of [[ME/CFS]] patients had elevated [[Autoantibody|autoantibodies]] to M3 and M4 [[muscarinic acetylcholine receptor]]s.<ref>{{Cite journal | last = Loebel|first = Madlen | last2 = Grabowski | first2 = Patricia | last3 = Heidecke | first3 = Harald | last4 = Bauer | first4 = Sandra | last5 = Hanitsch | first5 = Leif G. | last6 = Wittke | first6 = Kirsten | last7 = Meisel | first7 = Christian | last8 = Reinke | first8 = Petra | last9 = Volk | first9 = Hans-Dieter | date = Feb 2016 | title = Antibodies to β adrenergic and muscarinic cholinergic receptors in patients with Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/26399744|journal=Brain, Behavior, and Immunity|volume=52|pages=32–39|doi=10.1016/j.bbi.2015.09.013|issn=1090-2139|pmid=26399744}}</ref><ref>{{Cite web|url=http://www.meaction.net/2015/09/26/antibodies-found-in-subset-of-cfs-patients/ | title = Autoantibodies found in subset of CFS patients {{!}} #MEAction|website = [[The MEAction Network]]|language=en-US|access-date=2018-08-10}}</ref> A 2016 [[Australia|Australian]] study found that ME/CFS patients had significantly greater numbers of [[single nucleotide polymorphism]]s 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.<ref>{{Cite news | url=http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/ | title = A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise - Health Rising | last = Johnson | first =Cort | date = 2016-06-17|work=Health Rising|access-date=2018-08-26|archive-url=|archive-date=|url-status=|language=en-US}}</ref> 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.<ref>{{Cite journal | last = Oliveira | first = R.K. | date = 2016 | title=Pyridostigmine for Exercise Intolerance Treatment in Preload Failure|url=https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2016.193.1_MeetingAbstracts.A5664|journal=American Journal of Respiratory and Critical Care Medicine|volume=|pages=|via=}}</ref> 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).<ref name="Kawamura2003" /> == POTS == A small study of [[postural orthostatic tachycardia syndrome]] (POTS) in children found that 24.39% of patients had acetylcholine receptor autoantibodies.<ref>{{Cite journal | last = Li|first = Jiawei | last2 = Zhang | first2 = Qingyou | last3 = Liao | first3 = Ying | last4 = Zhang | first4 = Chunyu | last5 = Hao | first5 = Hongjun | last6 = Du | first6 = Junbao | date = 2014-08-03 | title = The Value of Acetylcholine Receptor Antibody in Children with Postural Tachycardia Syndrome|url=https://link.springer.com/article/10.1007/s00246-014-0981-8|journal=Pediatric Cardiology|language=en|volume=36|issue=1|pages=165–170|doi=10.1007/s00246-014-0981-8|issn=0172-0643}}</ref> A small study of adult patients found elevated α1, β1 and β2 adrenergic receptor autoantibodies.<ref>{{Cite journal | last = Li|first = Hongliang | last2 = Yu | first2 = Xichun | last3 = Liles | first3 = Campbell | last4 = Khan | first4 = Muneer | last5 = Vanderlinde‐Wood | first5 = Megan | last6 = Galloway | first6 = Allison | last7 = Zillner | first7 = Caitlin | last8 = Benbrook | first8 = Alexandria | last9 = Reim | first9 = Sean | date = 2014-01-27 | title = Autoimmune Basis for Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/abs/10.1161/JAHA.113.000755|journal=Journal of the American Heart Association|language=EN|volume=3|issue=1|doi=10.1161/jaha.113.000755|issn=2047-9980|pmc=3959717|pmid=24572257}}</ref> A small randomized crossover design trial found that patients with POTS improved with Mestinon.<ref>{{Cite journal | last = Raj|first = S.R. | date = 2005-05-31 | title = Acetylcholinesterase Inhibition Improves Tachycardia in Postural Tachycardia Syndrome|url=https://www.ahajournals.org/doi/pdf/10.1161/circulationaha.104.497594|journal=Circulation|volume=111|issue=21|pages=2734–2740|doi=10.1161/circulationaha.104.497594|issn=0009-7322}}</ref> == Ongoing clinical trials == === 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]], [[Myalgic encephalomyelitis|ME]], [[Chronic fatigue syndrome|CFS]], [[Fibromyalgia]] and [[Dyspnea]].<ref name="NCT03674541">{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT03674541 | title = The Exercise Response to Pharmacologic Cholinergic Stimulation in Preload Failure - NCT036745 | last = Systrom|first = David | authorlink=David Systrom | date = |website=Clinical trials|language=en|archive-url=|archive-date=|url-status=|access-date=2019-04-15}}</ref> 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.<ref name="NCT03674541" /> This trial is based on the theory that [[Small fiber peripheral neuropathy|small fiber neuropathy]] causes autonomic system dysfunction, resulting in breathlessness and post-exertional malaise.<ref name="NCT03674541" /> 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, [[:Category:Minnesota clinics|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." <ref name="POTStrial2019">{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT01370512 | title = Droxidopa / Pyridostigmine in Orthostatic Hypotension - ClinicalTrials.gov|website=clinicaltrials.gov|language=en|access-date=2019-04-15}}</ref> ===A Study of Pyridostigmine in Postural Tachycardia Syndrome=== A three-day trial involving 50 people with [[Postural orthostatic tachycardia syndrome|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.<ref name="POTSTrial2020">{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT00409435 | title = A Study of Pyridostigmine in Postural Tachycardia Syndrome - ClinicalTrials.gov|website=clinicaltrials.gov|language=en|access-date=2019-04-15}}</ref> == Side effects == Mestinon side effects that are most common include [[Gastrointestinal|gastrointestinal symptoms]] including abdominal cramps, [[diarrhea]] and bloating, a runny nose, [[Muscle fasciculations|muscle twitching]].<ref name="MGhope">{{Cite web|url=https://mghope.org/treatments | title = Treatments | last = ((Myasthenia Gravis Hope Foundation))|first = | authorlink = | date = 2017 | website = Myasthenia Gravis Hope Foundation|language=en-US|archive-url=|archive-date=|url-status=|access-date=2019-04-15}}</ref> Bradycardia, an abnormally slow heart rate may also occur, especially as a result of interaction with specific drugs.<ref name="medicines" /><ref name="drugscom" /><ref name="SmPC">{{Cite web|url=https://www.medicines.org.uk/emc/product/962/smpc | title = Mestinon 60mg Tablets - Summary of Product Characteristics (SmPC) - (eMC)|website=Electronic medicines compendium|access-date=2019-04-15}}</ref> === Gulf War Illness === Pyridostigmine was given to Gulf War personnel to protect them from nerve gas.<ref name="Golomb1999" /><ref>{{Cite book | title = Pyridostigmine Bromide|language=en | url =https://www.ncbi.nlm.nih.gov/books/NBK222848/ | date = 2000|publisher=National Academies Press (US)|first = | last = ((Institute of Medicine (US) Committee on Health Effects Associated with Exposures During the Gulf War)) | last2 = Fulco | first2 = Carolyn E. | last3 = Liverman | first3 = Catharyn T. | last4 = Sox | first4 = Harold C.}}</ref> 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.<ref>{{Cite web|url=https://youtu.be/OYKMMbPp_Do?t=546 | title = Dr. Robert Haley, What Caused Gulf War Illness | last = Haley|first = Robert | date = May 6, 2013 | website = YouTube|publisher=David Spencer|archive-url=|archive-date=|url-status=|access-date=}}</ref><ref>{{Cite news | url=https://www.newscientist.com/article/dn6157-gulf-war-veterans-have-fertility-problems/ | title = Gulf war veterans have fertility problems|work=New Scientist|access-date=2018-08-26|language=en-US}}</ref><ref name="Stencel2010">{{Cite web|url=http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=12835 | title = Gulf War Service Linked to Post-Traumatic Stress Disorder, Multisymptom Illness, Other Health Problems, But Causes Are Unclear | last = Stencel|first = Christine | last2 = Burnette | first2 = Alison | date = Apr 9, 2010 | website = |publisher=The National Academies of Sciences Engineering Medicine|language=en|archive-url=|archive-date=|url-status=|access-date=2018-08-26}}</ref><ref name="NS2004">{{Cite news | url=https://www.newscientist.com/article/dn6609-us-in-u-turn-over-gulf-war-syndrome/ | title = US in U-turn over Gulf war syndrome | last = MacKenzie | first = Debora | date = Nov 3, 2004|work=New Scientist|access-date=2018-08-26|archive-url=|archive-date=|url-status=|language=en-US}}</ref> Gulf War Illness, possible interactions with DEET, other pesticides or organic solvents are not mentioned in the patient information.<ref name="medicines" /><ref name="drugscom">{{Cite web|url=https://www.drugs.com/sfx/mestinon-side-effects.html | title = Mestinon Side Effects in Detail|website=Drugs.com|language=en|access-date=2019-04-15}}</ref> === 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.<ref name="Golomb1999">{{Cite web|url=https://www.rand.org/pubs/monograph_reports/MR1018z2.html | title = A Review of the Scientific Literature As It Pertains to Gulf War Illnesses | last = Golomb|first = Beatrice A. | authorlink = | date = 1999 | website = |series=Volume 2: Pyridostigmine Bromide|publisher=RAND Corporation|location=Santa Monica, CA|archive-url=|archive-date=|url-status=|access-date=}}</ref> Increased chemical sensitives are not referred to in the patient information leaflet.<ref name="medicines">{{Cite web|url=https://www.medicines.org.uk/emc/files/pil.962.pdf | title=Mestinon patient info | last = Mylan | first = | authorlink = | date = 2018 | website = Electronic medicines compendium|archive-url=|archive-date=|url-status=|access-date=Apr 15, 2019}}</ref><ref name="drugscom" /> === Overdose risk === Overdose can cause a "cholinergic crisis", which can be very dangerous.<ref name="MGhope" /><ref name="SmPC" /> == Interviews and presentations == *2018, [https://youtu.be/FMaKfv8peww?t=1363 Advancements in ME/CFS Research, David M. Systrom, MD; Brigham and Women's Hospital | ME/CFSAlert 98]<ref>{{Cite web|url=https://youtu.be/FMaKfv8peww?t=1363 | title = Advancements in ME/CFS Research, David M. Systrom, MD; Brigham and Women's Hospital | last = Systrom|first = David M. | date = Jul 2, 2018 | website = YouTube|publisher=ME/CFS Alert|archive-url=|archive-date=|url-status=|access-date=}}</ref> == Notable studies == * 2003, Efficacy of a half dose of oral pyridostigmine in the treatment of chronic fatigue syndrome: three case reports<ref name="Kawamura2003" /> [http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.587.6854&rep=rep1&type=pdf (Full text)] == See also == * [[Post-exertional malaise]] * [[Exercise]] * [[Bromide]] ==Learn more== *[[David Systrom]] *[https://livingwithchronicfatiguesyndrome.wordpress.com/2017/09/13/mestinon-for-me/ Mestinon for ME] - personal experience of the drug *[http://www.healthrising.org/blog/2016/06/17/mestinon-chronic-fatigue-vagus-nerve-stimulation-exercise/ A Mestinon Miracle: Vagus Nerve Stimulating Drug Helps Long Time ME/CFS Patient Exercise] - Cort Johnson *[https://www.drugs.com/mtm/pyridostigmine.html Pyridostigmine] - drugs.com *[https://www.medicines.org.uk/emc/product/962/smpc Pyridostigmine] - UK medicines information *[https://www.medicines.org.uk/emc/files/pil.962.pdf Pyridostigmine] - patient information leaflet (UK) *[http://www.mghope.org/treatments Treatments for Myasthenia Gravis] - Myasthenia Gravis Hope ==References== {{Reflist}} [[Category:Potential treatments]]
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