Pyridostigmine is a medication used to treat

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, ...

and underactive bladder. It is also used together with

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is also used off-label to treat some forms of

Postural orthostatic tachycardia syndrome Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon sitting up or standing. POTS is a disorder of the autonomic nervous system that can lead to a variety of symptoms, ...

. It is typically given

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

but can also be used by injection. The effects generally begin within 45 minutes and last up to 4 hours. Common side effects include nausea, diarrhea, frequent urination, and abdominal pain. More severe side effects include low blood pressure, weakness, and

allergic reactions Allergies, also known as allergic diseases, are various conditions caused by hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic dermatitis, alle ...

. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is safe for the fetus. Pyridostigmine is an

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...

in the

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation ...

family of medications. It works by blocking the action of

acetylcholinesterase Acetylcholinesterase (HUGO Gene Nomenclature Committee, HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme th ...

and therefore increases the levels of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

. 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 WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Pyridostigmine is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

Medical uses

Pyridostigmine is used to treat muscle weakness in people with

or forms of

congenital myasthenic syndrome Congenital myasthenic syndrome (CMS) is an inherited neuromuscular disorder caused by defects of several types at the neuromuscular junction. The effects of the disease are similar to Lambert-Eaton Syndrome and myasthenia gravis, the difference ...

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 Soman (or GD, EA 1210, Zoman, PFMP, A-255, systematic name: ''O''-pinacolyl methylphosphonofluoridate) is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibit ...

in order to increase survival. Used in particular during the first

Gulf War , combatant2 = , commander1 = , commander2 = , strength1 = Over 950,000 soldiers3,113 tanks1,800 aircraft2,200 artillery systems , page = https://www.govinfo.gov/content/pkg/GAOREPORTS-PEMD-96- ...

, pyridostigmine bromide has been implicated as a causal factor in Gulf War syndrome. With pyridostigmine classified as a type of

parasympathomimetic A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...

, it can be used to treat underactive bladder. Pyridostigmine sometimes is used to treat

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

. It may also be of benefit in chronic axonal

polyneuropathy Polyneuropathy () is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands and feet and may prog ...

. It is also being prescribed

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

for

postural orthostatic tachycardia syndrome Postural orthostatic tachycardia syndrome (POTS) is a condition characterized by an abnormally large increase in heart rate upon sitting up or standing. POTS is a disorder of the autonomic nervous system that can lead to a variety of symptoms, ...

(POTS) as well as complications resulting from

Ehlers–Danlos syndrome Ehlers–Danlos syndromes (EDS) is a group of 14 genetic connective-tissue disorders. Symptoms often include loose joints, joint pain, stretchy velvety skin, and abnormal scar formation. These may be noticed at birth or in early childhood. Co ...

Contraindications

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

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 Additional side effects include: * Muscle twitching * Muscle cramps and weakness

Mechanism of action

Pyridostigmine is an

. It

inhibit Inhibitor or inhibition may refer to: Biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotransmi ...

in the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in neuromuscular junction, muscles or glands. Chemical synapses allow neurons to form biological neural ...

, thus slowing down the

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

. Like its predecessor

neostigmine Neostigmine, sold under the brand name Bloxiverz, among others, is a medication used to treat myasthenia gravis, Ogilvie syndrome, and urinary retention without the presence of a blockage. It is also used in anaesthesia to end the effects of n ...

, it is a quaternary

carbamate In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...

inhibitor of cholinesterase that does not cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. It carbamylates about 30% of peripheral cholinesterase enzyme, and the carbamylated enzyme eventually regenerates by natural hydrolysis and excess acetylcholine (ACh) levels revert to normal. The ACh diffuses across the synaptic cleft and binds to receptors on the post synaptic membrane, causing an influx of

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

(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

is present in the endplate membrane close to the receptors on the post synaptic membrane, and quickly hydrolyses ACh.

Names

Pyridostigmine bromide is available under the trade name Mestinon (

Valeant Pharmaceuticals Bausch Health Companies Inc. is a global, diversified American-Canadian pharmaceutical company. Its global corporate headquarters are located in Laval, Quebec, Canada, and its U.S. headquarters are in Bridgewater, New Jersey. It develops, manufa ...

), Regonol and Gravitor (SUN Pharma).

References

External links

* {{Portal bar, Medicine Acetylcholinesterase inhibitors Aromatic carbamates Dimethylamino compounds Peripherally selective drugs Pyridinium compounds Wikipedia medicine articles ready to translate World Health Organization essential medicines