Pyridostigmine

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Pyridostigmine
Pyridostigmine.svg
Pyridostigmine ball-and-stick.png
Systematic (IUPAC) name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade namesMestinon
AHFS/Drugs.commonograph
MedlinePlusa682229
Pregnancy cat.C (AU) C (US)
Legal statusPOM (UK) -only (US)
RoutesOral, intravenous
Pharmacokinetic data
Bioavailability7.6 +/- 2.4%
Half-life1.78 +/- 0.24hrs
ExcretionRenal
Identifiers
CAS number155-97-5 YesY
ATC codeN07AA02
PubChemCID 4991
DrugBankDB00545
ChemSpider4817 YesY
UNII19QM69HH21 YesY
KEGGD00487 YesY
ChEMBLCHEMBL1115 YesY
Chemical data
FormulaC9H13N2O2 
Mol. mass181.212 g/mol
 YesY (what is this?)  (verify)
 
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Pyridostigmine
Pyridostigmine.svg
Pyridostigmine ball-and-stick.png
Systematic (IUPAC) name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade namesMestinon
AHFS/Drugs.commonograph
MedlinePlusa682229
Pregnancy cat.C (AU) C (US)
Legal statusPOM (UK) -only (US)
RoutesOral, intravenous
Pharmacokinetic data
Bioavailability7.6 +/- 2.4%
Half-life1.78 +/- 0.24hrs
ExcretionRenal
Identifiers
CAS number155-97-5 YesY
ATC codeN07AA02
PubChemCID 4991
DrugBankDB00545
ChemSpider4817 YesY
UNII19QM69HH21 YesY
KEGGD00487 YesY
ChEMBLCHEMBL1115 YesY
Chemical data
FormulaC9H13N2O2 
Mol. mass181.212 g/mol
 YesY (what is this?)  (verify)

Pyridostigmine is a parasympathomimetic and a reversible cholinesterase inhibitor. Since it is a quaternary amine, it is poorly absorbed in the gut and does not cross the blood–brain barrier, except possibly in stressful conditions.[1]

Mode of action[edit]

In a synapse, action potentials are conducted along motor nerves to their terminals where they initiate a Ca2+ influx and the release of acetylcholine (ACh). The ACh diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of Na+ and an efflux of K+ ions, resulting in depolarization. If large enough, this depolarization results in an action potential. To prevent constant stimulation once the ACh is released, an enzyme called acetylcholinesterase is present in the endplate membrane close to the receptors on the post synaptic membrane, and quickly hydrolizes ACh.

Pyridostigmine inhibits acetylcholinesterase in the synaptic cleft, thus slowing down the hydrolysis of acetylcholine. It is a quaternary carbamate inhibitor of cholinesterase that does not cross the blood–brain barrier which carbamylates about 30% of peripheral cholinesterase enzyme. The carbamylated enzyme eventually regenerates by natural hydrolysis and excess ACh levels revert to normal.

Clinical uses[edit]

Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis and to combat the effects of curariform drug toxicity. Pyridostigmine bromide has been FDA approved for military use during combat situations as an agent to be given prior to exposure to the nerve agent Soman in order to increase survival. Used in particular during the first Gulf War, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome.[2]

Pyridostigmine sometimes is used to treat orthostatic hypotension.[3] It may also be of benefit in chronic axonal polyneuropathy. [4]

It is also being prescribed 'off-label' for the postural tachycardia syndrome[5][6]

Pyridostigmine bromide is available under the trade names Mestinon (Valeant Pharmaceuticals) and Regonol.

Contraindications[edit]

Pyrostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.[7][8]

Side effects[edit]

Common side effects include:[7]

Chemistry[edit]

Pyridostigmine, 3-[(dimethylaminocarbonyl)oxy]-1-methyl pyridinium bromide, is synthesized from 3-hydroxypyridine, which is reacted with dimethylaminocarbamoyl chloride, which gives 3-(dimethylaminocarbamoyl)pyridine. The last is reacted with methylbromide, giving pyridostigmine.

Pyridostigmine synthesis.png

References[edit]

  1. ^ Gulf War Syndrome: More Complex Than Middle East Politics. JWatch Psychiatry 1997;1997:15-15.
  2. ^ Golomb, B. (2008) "Acetylcholinesterase inhibitors and Gulf War illnesses" Proc Natl Acad Sci; Reuters; MedPageToday.com
  3. ^ Gales BJ, Gales MA. (2007). "Pyridostigmine in the treatment of orthostatic intolerance". Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509. 
  4. ^ Galassi G, et al. (2011). "Pyridostigmine in the treatment of orthostatic intolerance". J Clin Neuromusc Dis. 12 (4): 223–226. doi:10.1097/CND.0b013e3181df2b18. 
  5. ^ http://www.ncbi.nlm.nih.gov/pubmed/21410722
  6. ^ http://www.theannals.com/content/41/2/314.abstract
  7. ^ a b Mestinon | Home
  8. ^ Mestinon Official FDA information, side effects and uses

Related publications[edit]

  1. Brenner, G. M. (2000). Pharmacology. Philadelphia, PA: W.B. Saunders Company. ISBN 0-7216-7757-6
  2. Canadian Pharmacists Association (2000). Compendium of Pharmaceuticals and Specialties (25th ed.). Toronto, ON: Webcom. ISBN 0-919115-76-4
  3. Neal, M.J. (2002). Medical Pharmacology at a Glance (5th ed.). London, England: Blackwell Publishing. ISBN 1-4051-3360-0