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.[12]
Neostigmine is often prescribed for underactive urinary bladder.[13]
Hospitals sometimes administer a solution containing neostigmine intravenously to delay the effects of envenomation through snakebite.[14] Some promising research results have also been reported for administering the drug nasally in order to buy time if anti-venom is not immediately available.[15]
Side effects
Neostigmine has a wide variety of side-effects due to its action that increases acetylcholine (ACh) binding muscarinic receptors on exocrine glandular cells throughout the body, cardiac muscle cells, and smooth muscle cells. These effects include: salivation, lacrimation, diarrhea, bradycardia, and bronchoconstriction.[16] Gastrointestinal symptoms occur earliest.[17]: 109
For this reason, it is usually given along with an anti-cholinergic drug such as atropine or glycopyrrolate which act only on muscarinic receptors while permitting neostigmine action at nicotinic receptors.[18]
Neostigmine can also induce generic ocular side effects including: headache, brow pain, blurred vision, phacodonesis, pericorneal injection, congestive iritis, various allergic reactions, and rarely, retinal detachment.[17]: 114
Pharmacology
Acetylcholine is metabolized by the enzyme acetylcholinesterase that cleaves acetylcholine in the neuromuscular junction into acetate and choline. Neostigmine is an inhibitor of acetylcholinesterase. 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.
Its action leads to the accumulation of acetylcholine in the neuromuscular junction that compete with the non-depolarizing blocker agent bound to the acetylcholine receptors. By interfering with the breakdown of acetylcholine, neostigmine indirectly stimulates both nicotinic and muscarinic receptors.[10]
Neostigmine is administered intravenously. The drug should be administered when a peripheral nerve stimulator shows a second twitch is present or when the first twitch response is considerably above 10% of baseline. Peak effect is at 7 to 10 minutes.[10] Neostigmine has moderate duration of action – usually two to four hours.[20] It is metabolized by enzymes in the liver and excreted in the urine.[10]
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.[21]
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.[22]
History
Neostigmine was first synthesized by Aeschlimann and Reinert in 1931[23] and was patented by Aeschlimann in 1933.[24]
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.[17]: 103
^ abcdefghijk"Neostigmine Bromide". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
^World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
^Howard J, Wigley J, Rosen G, D'mello J (February 2017). "Glycopyrrolate: It's time to review". Journal of Clinical Anesthesia. 36: 51–53. doi:10.1016/j.jclinane.2016.09.013. PMID28183573.
^Abdelaal Ahmed Mahmoud A, Mansour AZ, Yassin HM, Hussein HA, Kamal AM, Elayashy M, et al. (December 2018). "Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial". Anesthesia and Analgesia. 127 (6): 1434–1439. doi:10.1213/ANE.0000000000003734. PMID30169405. S2CID52142441.
^Porst H, Kny L (May 1985). "[The structure of degradation products of neostigmine bromide]". Die Pharmazie (in German). 40 (5): 325–328. PMID4034636.
^Ferdous AJ, Waigh RD (June 1993). "Application of the WATR technique for water suppression in 1H NMR spectroscopy in determination of the kinetics of hydrolysis of neostigmine bromide in aqueous solution". The Journal of Pharmacy and Pharmacology. 45 (6): 559–562. doi:10.1111/j.2042-7158.1993.tb05598.x. PMID8103105. S2CID38613106.
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