neostigmine

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.{{cite book | chapter-url= https://www.ncbi.nlm.nih.gov/books/NBK470596/ | pmid=29261883 | year=2022 | vauthors = Neely GA, Sabir S, Kohli A | chapter = Neostigmine | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing }}{{cite web | url=https://www.drugs.com/cdi/neostigmine-injection.html | title=Neostigmine Injection: Indications, Side Effects, Warnings | work = Drugs.com }}

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.{{cite journal | vauthors = Maloney N, Vargas HD | title = Acute intestinal pseudo-obstruction (Ogilvie's syndrome) | journal = Clinics in Colon and Rectal Surgery | volume = 18 | issue = 2 | pages = 96–101 | date = May 2005 | pmid = 20011348 | pmc = 2780141 | doi = 10.1055/s-2005-870890 }}

Neostigmine is often prescribed for underactive urinary bladder.{{cite journal | vauthors = Moro C, Phelps C, Veer V, Clark J, Glasziou P, Tikkinen KA, Scott AM | title = The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis | journal = Neurourology and Urodynamics | volume = 41 | issue = 1 | pages = 127–139 | date = January 2022 | pmid = 34816481 | doi = 10.1002/nau.24839 | s2cid = 244530010 | url = https://pure.bond.edu.au/ws/files/118955227/AM_The_effectiveness_of_parasympathomimetics_for_treating.pdf }}

Hospitals sometimes administer a solution containing neostigmine intravenously to delay the effects of envenomation through snakebite.{{cite web | vauthors = Franklin D | url = https://www.npr.org/blogs/health/2013/07/30/207050435/potential-treatment-for-snakebites-leads-to-a-paralyzing-test | title = Potential Treatment For Snakebites Leads To A Paralyzing Test | work = NPR | archive-url = https://web.archive.org/web/20140809234546/http://www.npr.org/blogs/health/2013/07/30/207050435/potential-treatment-for-snakebites-leads-to-a-paralyzing-test | archive-date= 9 August 2014 | date = 31 July 2013 }} 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.{{cite journal | vauthors = Bulfone TC, Samuel SP, Bickler PE, Lewin MR | title = Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite | journal = Journal of Tropical Medicine | volume = 2018 | pages = 4320175 | date = 2018 | pmid = 30154870 | pmc = 6091453 | doi = 10.1155/2018/4320175 | doi-access = free }}

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.{{cite book | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK557541/ | pmid=32491473 | year=2022 | vauthors = Naji A, Gatling JW | chapter = Muscarinic Antagonists | title = StatPearls [Internet]. | location = Treasure Island (FL) | publisher = StatPearls Publishing }} Gastrointestinal symptoms occur earliest.{{rp|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.{{cite journal | vauthors = Howard J, Wigley J, Rosen G, D'mello J | title = Glycopyrrolate: It's time to review | journal = Journal of Clinical Anesthesia | volume = 36 | pages = 51–53 | date = February 2017 | pmid = 28183573 | doi = 10.1016/j.jclinane.2016.09.013 }}

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.{{cite book | vauthors = Gilman AG, Goodman LS, Gilman Sr A |author-link1=Alfred G. Gilman |author-link2=Louis S. Goodman |author-link3=Alfred Gilman, Sr. | name-list-style = vanc |title=Goodman & Gilman's The Pharmacological Basis of Therapeutics |edition=6th |publisher=Macmillan Publishing Co., Inc. |location=New York |year=1980 |title-link=Goodman & Gilman's The Pharmacological Basis of Therapeutics }}{{rp|114}}

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.

Unlike physostigmine, neostigmine has a quaternary nitrogen; hence, it is more polar. It does not cross the blood–brain barrier and enter the CNS.{{cite journal | vauthors = Abdelaal Ahmed Mahmoud A, Mansour AZ, Yassin HM, Hussein HA, Kamal AM, Elayashy M, Elemady MF, Elkady HW, Mahmoud HE, Cusack B, Hosny H, Abdelhaq M | display-authors = 6 | title = Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial | language = en-US | journal = Anesthesia and Analgesia | volume = 127 | issue = 6 | pages = 1434–1439 | date = December 2018 | pmid = 30169405 | doi = 10.1213/ANE.0000000000003734 | s2cid = 52142441 }}

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. Neostigmine has moderate duration of action – usually two to four hours.{{cite book | vauthors = Howland RD, Mycek MJ, Harvey RA, Champe PC, Mycek MJ | title = Pharmacology | edition = 3rd | publisher = Lippincott's Illustrated Reviews | date = 2008 | page = 51 }} It is metabolized by enzymes in the liver and excreted in the urine.

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.{{cite journal | vauthors = Porst H, Kny L | title = [The structure of degradation products of neostigmine bromide] | language = de | journal = Die Pharmazie | volume = 40 | issue = 5 | pages = 325–328 | date = May 1985 | pmid = 4034636 }}

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.{{cite journal | vauthors = Ferdous AJ, Waigh RD | title = 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 | journal = The Journal of Pharmacy and Pharmacology | volume = 45 | issue = 6 | pages = 559–562 | date = June 1993 | pmid = 8103105 | doi = 10.1111/j.2042-7158.1993.tb05598.x | s2cid = 38613106 }}

Neostigmine was first synthesized by Aeschlimann and Reinert in 1931{{cite book| vauthors = Whitacre DM |title=Reviews of Environmental Contamination and Toxicology|url=https://books.google.com/books?id=PCIbhO_xlcEC&pg=PA57|year=2007|publisher=Springer Science+Business Media|isbn=978-0-387-73162-9|page=57}} and was patented by Aeschlimann in 1933.{{cite patent | inventor = Aeschliman JA | country = US | number = 1905990 | gdate = 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.{{rp|103}}

{{Reflist}}

• {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/rn/59-99-4 | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Neostigmine }}
• {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/neostigmine%20methylsulfate | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Neostigmine methylsulfate }}
• {{cite web| url = https://druginfo.nlm.nih.gov/drugportal/name/neostigmine%20bromide | publisher = U.S. National Library of Medicine| work = Drug Information Portal| title = Neostigmine bromide }}

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