Pyridostigmine

Pyridostigmine
Pyridostigmine
Systematic (IUPAC) name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade names Mestinon
AHFS/Drugs.com monograph
MedlinePlus a682229
Pregnancy cat. C(AU) C(US)
Legal status POM (UK) ℞-only (US)
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability 7.6 +/- 2.4%
Half-life 1.78 +/- 0.24hrs
Excretion Renal
Identifiers
CAS number 155-97-5 YesY
ATC code N07AA02
PubChem CID 4991
DrugBank APRD00380
ChemSpider 4817 YesY
UNII 19QM69HH21 N
KEGG D00487 N
ChEMBL CHEMBL1115 YesY
Chemical data
Formula C9H13N2O2 
Mol. mass 181.212 g/mol
SMILES eMolecules & PubChem
 N(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]

Contents

Mode of action

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 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, and is taken daily in anticipation of an attack, 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

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 is now also used to treat orthostatic hypotension.[3]

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

Contraindications

Pyrostigmine bromide is contraindicated in cases of mechanical intestinal or urinary obstruction and should be used with caution in patients with bronchial asthma.[4][5]

Side effects

Common side effects include:[4]

  • Sweating
  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal cramps
  • Increased salivation
  • Tearing
  • Increased bronchial secretions
  • Constricted pupils
  • Facial flushing due to vasodilation
  • Erectile dysfunction

Chemistry

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

  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". Ann Pharmacother. 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509. 
  4. ^ a b Mestinon | Home
  5. ^ Mestinon Official FDA information, side effects and uses

Related publications

  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 1405133600

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Look at other dictionaries:

  • Pyridostigmine — Structure de la pyridostigmine Général Nom IUPAC 3 [(diméthylcarbamoyl)oxy] 1 méthylpyridinium …   Wikipédia en Français

  • pyridostigmine — noun see pyridostigmine bromide …   New Collegiate Dictionary

  • pyridostigmine bromide — noun Etymology: International Scientific Vocabulary pyridine + neostigmine Date: 1961 a cholinergic drug C9H13BrN2O2 used especially in the treatment of myasthenia gravis and as a prophylactic against the effects of nerve gas called also… …   New Collegiate Dictionary

  • pyridostigmine — noun A parasympathomimetic and reversible cholinesterase inhibitor, used to treat muscle weakness and to combat the effects of curariform drug toxicity …   Wiktionary

  • pyridostigmine — pyr·i·do·stig·mine .pir əd ō stig .mēn n a cholinergic drug that is administered in the form of its bromide C9H13BrN2O2 esp. in the treatment of myasthenia gravis see MESTINON * * * n. an anticholinesterase drug used in the treatment of… …   Medical dictionary

  • pyridostigmine — [ˌpɪrɪdə(ʊ) stɪgmi:n] noun Medicine a synthetic compound related to neostigmine, with similar but weaker and longer acting effects. Origin 1950s: blend of pyridine and neostigmine …   English new terms dictionary

  • pyridostigmine — n. an anticholinesterase drug used in the treatment of myasthenia gravis. It is administered by mouth; side effects may include nausea, vomiting, abdominal pain, diarrhoea, sweating, and increased salivation. Trade names: Mestinon …   The new mediacal dictionary

  • pyridostigmine —  n.f. Antidote utilisé pour se protéger des effets de certains gaz de combat …   Le dictionnaire des mots absents des autres dictionnaires

  • pyridostigmine — …   Useful english dictionary

  • pyridostigmine bromide — /pir i doh stig meen/, Pharm. a cholinesterase inhibitor, C9H13BrN2O2, used in its bromide form in the treatment of myasthenia gravis. [1960 65; PYRID(INE) + O + (PHYSO)STIGMINE] * * * …   Universalium

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