Pyridostigmine

Pyridostigmine

Systematic (IUPAC) name
3-[(dimethylcarbamoyl)oxy]-1-methylpyridinium
Clinical data
Trade names	Mestinon
AHFS/Drugs.com	monograph
MedlinePlus	a682229
Pregnancy category	AU: C US: C (Risk not ruled out)
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral, intravenous
Pharmacokinetic data
Bioavailability	7.6 +/- 2.4%
Biological half-life	1.78 +/- 0.24hrs
Excretion	Renal
Identifiers
CAS Number	155-97-5 Y
ATC code	N07AA02 (WHO)
PubChem	CID: 4991
DrugBank	DB00545 Y
ChemSpider	4817 Y
UNII	19QM69HH21 Y
KEGG	D00487 Y
ChEMBL	CHEMBL1115 Y
Chemical data
Formula	C9H13N2O2
Molecular mass	181.212 g/mol
SMILES O=C(Oc1ccc[n+](c1)C)N(C)C
InChI InChI=1S/C9H13N2O2/c1-10(2)9(12)13-8-5-4-6-11(3)7-8/h4-7H,1-3H3/q+1 Y Key:RVOLLAQWKVFTGE-UHFFFAOYSA-N Y
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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.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

Medical 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.

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

It is also being prescribed 'off-label' for the postural tachycardia syndrome as well as complications resulting from Ehlers-Danlos Syndrome.

Contraindications

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

Side effects

Common side effects include:

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

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.

Names

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

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