Pyridostigmine

Pyridostigmine
Systematic (IUPAC) name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade names Mestinon
AHFS/Drugs.com monograph
MedlinePlus a682229
  • AU: C
  • US: C (Risk not ruled out)
Oral, intravenous
Pharmacokinetic data
Bioavailability 7.6 +/- 2.4%
Half-life 1.78 +/- 0.24hrs
Excretion Renal
Identifiers
155-97-5 Yes
N07AA02
PubChem CID 4991
DrugBank DB00545 Yes
ChemSpider 4817 Yes
UNII 19QM69HH21 Yes
KEGG D00487 Yes
ChEMBL CHEMBL1115 Yes
Chemical data
Formula C9H13N2O2
181.212 g/mol
 Yes (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 cannot penetrate across the blood–brain barrier.[1]

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+, 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 hydrolyses 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

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

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

Common side effects include:[7]

  • 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.

References

  1. ↑ Amourette C, Lamproglou I, Barbier L et al. (November 2009). "Gulf War illness: Effects of repeated stress and pyridostigmine treatment on blood-brain barrier permeability and cholinesterase activity in rat brain". Behavioural Brain Research 203 (2): 207–14. doi:10.1016/j.bbr.2009.05.002. PMID 19433115.
  2. ↑ Golomb BA (March 2008). "Acetylcholinesterase inhibitors and Gulf War illnesses". Proceedings of the National Academy of Sciences of the United States of America 105 (11): 4295–300. Bibcode:2008PNAS..105.4295G. doi:10.1073/pnas.0711986105. JSTOR 25461411. PMC 2393741. PMID 18332428. Lay summary – Reuters (March 10, 2008).
  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. ↑ Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.
  5. ↑ Kanjwal K, Karabin B, Sheikh M et al. (June 2011). "Pyridostigmine in the treatment of postural orthostatic tachycardia: a single-center experience". Pacing and Clinical Electrophysiology 34 (6): 750–5. doi:10.1111/j.1540-8159.2011.03047.x. PMID 21410722.
  6. ↑ Gales BJ, Gales MA (February 2007). "Pyridostigmine in the treatment of orthostatic intolerance". The Annals of Pharmacotherapy 41 (2): 314–8. doi:10.1345/aph.1H458. PMID 17284509.
  7. ↑ 7.0 7.1 Mestinon | Home
  8. ↑ 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 1-4051-3360-0