|Trade names||Mestinon, others|
|by mouth, intravenous|
|Bioavailability||7.6 +/- 2.4%|
|Biological half-life||1.78 +/- 0.24hrs|
|Chemical and physical data|
|Molar mass||181.212 g/mol|
|3D model (Jmol)|
Pyridostigmine is medication used to treat myasthenia gravis. It is also used together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is typically given by mouth but can also be used by injection. The effects generally begin within 45 minutes and last up to 6 hours.
Common side effects include nausea, diarrhea, frequent urination, and abdominal pain. More severe side effects include low blood pressure, weakness, and allergic reactions. It is unclear if use in pregnancy is safe for the baby. Pyridostigmine is an acetylcholinesterase inhibitor in the cholinergic family of medications. It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.
Pyridostigmine was patented in 1945 and came into medical use in 1955. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. Pyridostigmine is available as a generic medication. The wholesale cost in the developing world is about 7.17 to 65.93 USD a month. In the United States it costs about 25 to 50 USD per month.
Pyridostigmine is used to treat muscle weakness in people with myasthenia gravis or forms of congenital myasthenic syndrome 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.
Common side effects include:
- Abdominal cramps
- Increased salivation
- Increased bronchial secretions
- Constricted pupils
- Facial flushing due to vasodilation
- Erectile dysfunction
Mechanism 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.
Pyridostigmine bromide is available under the trade names Mestinon (Valeant Pharmaceuticals), Regonol and Gravitor (SUN Pharma).
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