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 non-depolarising neuromuscular blocking medication. 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 Organizations List of Essential Medicines. The term is from Greek neos, meaning "new", and "-stigmine", in reference to its parent molecule, physostigmine, on which it is based.

Medical uses
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.Another indication for use is the conservative management of acute colonic pseudo-obstruction, or Ogilvies 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.

Side effects
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.: 114  Neostigmine is often prescribed for underactive urinary bladder.Neostigmine has a wide variety of side-effects such as reduced heart rate (bradycardia), due to the increase of acetylcholine at nerve terminals. For this reason it is usually given along with an anti-cholinergic drug such as atropine or glycopyrrolate.Gastrointestinal symptoms occur earliest after ingestion and include anorexia, nausea, vomiting, abdominal cramps, and diarrhea.: 109

Pharmacology
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. It does not cross the blood–brain barrier and enter the CNS. However, 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 ester site of acetylcholinesterase, which blocks the enzyme from breaking 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.

Chemistry
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.

Spectral data
Neostigmine shows notable UV/VIS absorption at 261 nm, 267 nm, and 225 nm.Neostigmines 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.

History
Neostigmine was first synthesized by Aeschlimann and Reinert in 1931 and was patented by Aeschlimann in 1933.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.: 103

References
External links
"Neostigmine". Drug Information Portal. U.S. National Library of Medicine.
"Neostigmine methylsulfate". Drug Information Portal. U.S. National Library of Medicine.
"Neostigmine bromide". Drug Information Portal. U.S. National Library of Medicine.