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|Trade names||Prostigmin, Vagostigmin, others|
|IM, IV, subcutaneous, by mouth|
|Bioavailability||Unclear, probably less than 5%|
|Metabolism||Slow hydrolysis by acetylcholinesterase and also by plasma esterases|
|Onset of action||Within 30 min (injection), with 4 hrs (by mouth)|
|Elimination half-life||50–90 minutes|
|Duration of action||up to 4 hrs|
|Excretion||Unchanged drug (up to 70%) and alcoholic metabolite (30%) are excreted in the urine|
|Chemical and physical data|
|Molar mass||223.30 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Neostigmine, sold under the brand name Prostigmin 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 together with atropine to end the effects of neuromuscular blocking medication of the non-depolarizing type. It is given by injection either into a vein, muscle, or under the skin. After injection effects are generally greatest within 30 minutes and last up to 4 hours.
Common side effects include nausea, increased saliva, crampy abdominal pain, and slow heart rate. More severe side effects include low blood pressure, weakness, and allergic reactions. It is unclear if use in pregnancy is safe for the baby. Neostigmine is in the cholinergic family of medications. It works by blocking the action of acetylcholinesterase and therefore increases the levels of acetylcholine.
Neostigmine was patented in 1931. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. The wholesale cost in the developing world is about US$0.18–2.6 per dose. The term is from Greek neos, meaning "new", and "-stigmine", in reference to its parent molecule, physostigmine, on which it is based.
It is used to improve muscle tone in people with myasthenia gravis, and also to reverse the effects of non-depolarizing muscle relaxants such as rocuronium and vecuronium at the end of an operation, usually in a dose of 25 to 50 μg per kilogram.
Another indication for use is the conservative management of acute colonic pseudo-obstruction, or Ogilvie's syndrome, in which patients get massive colonic dilatation in the absence of a true mechanical obstruction.
Hospitals sometimes administer a solution containing neostigmine intravenously to delay the effects of envenomation through snakebite. Some promising research results have also been reported for administering the drug nasally as a snakebite treatment. Neostigmine was approved in 2015 in the United States to reverse the effects of muscle relaxants.
Neostigmine can induce generic ocular side effects including: headache, brow pain, blurred vision, phacodonesis, pericorneal injection, congestive iritis, various allergic reactions, and rarely, retinal detachment.
Gastrointestinal symptoms occur earliest after ingestion and include anorexia, nausea, vomiting, abdominal cramps, and diarrhea.
By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors. Unlike physostigmine, neostigmine has a quaternary nitrogen; hence, it is more polar and does not cross the blood–brain barrier and enter the CNS, but it does cross the placenta. Its effect on skeletal muscle is greater than that of physostigmine. Neostigmine has moderate duration of action – usually two to four hours. Neostigmine binds to the anionic and esteric site of cholinesterase. The drug blocks the active site of acetylcholinesterase so the enzyme can no longer break down the acetylcholine molecules before they reach the postsynaptic membrane receptors. This allows for the threshold to be reached so a new impulse can be triggered in the next neuron. In myasthenia gravis there are too few acetylcholine receptors so with the acetylcholinesterase blocked, acetylcholine can bind to the few receptors and trigger a muscular contraction.
Neostigmine, which can be viewed as a simplified analog of physostigmine, is made by reacting 3-dimethylaminophenol with N-dimethylcarbamoyl chloride, which forms the dimethylcarbamate, and its subsequent alkylation using dimethyl sulfate forming the desired compound.
Neostigmine shows notable UV/VIS absorption at 261 nm, 267 nm, and 225 nm.
Neostigmine's 1H NMR Spectroscopy reveals shifts at: 7.8, 7.7, 7.4, 7.4, 3.8, and 3.1 parts per million. The higher shifts are due to the aromatic hydrogens. The lower shifts at 3.8 ppm and 3.1 ppm are due to the electronic withdrawing nature of the tertiary and quaternary nitrogen, respectively.
Neostigmine is made by first reacting 3-dimethylaminophenol with N-dimethylcarbamoyl chloride, which forms a dimethylcarbamate. Next, that product is alkylated using dimethyl sulfate, which forms neostigmine.