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| Trade names | Bloxiverz, Prostigmin, Vagostigmin, others |
| AHFS/Drugs.com | Monograph |
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| Routes of administration | Intramuscular,intravenous,subcutaneous,by mouth |
| Drug class | Cholinesterase inhibitor |
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| Pharmacokinetic data | |
| Bioavailability | Unclear, probably less than 5% |
| Metabolism | Slow hydrolysis by acetylcholinesterase and also by plasma esterases |
| Onset of action | Within 10-20 min (injection),[3] with 4 hrs (by mouth)[citation needed] |
| Eliminationhalf-life | 50–90 minutes |
| Duration of action | up to 4 hrs[3] |
| Excretion | Unchanged drug (up to 70%) and alcoholic metabolite (30%) are excreted in the urine |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.305.602 |
| Chemical and physical data | |
| Formula | C12H19N2O2+ |
| Molar mass | 223.296 g·mol−1 |
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Neostigmine, sold under the brand nameBloxiverz, among others, is amedication used to treatmyasthenia gravis,Ogilvie syndrome, andurinary retention without the presence of a blockage.[3][4] It is also used in anaesthesia to end the effects of non-depolarisingneuromuscular blocking medication.[3] It is given by injection eitherinto a vein,muscle, orunder the skin.[3] After injection effects are generally greatest within 30 minutes and last up to 4 hours.[3][5]
Common side effects include nausea, increased saliva, crampy abdominal pain, andslow heart rate.[3] More severe side effects includelow blood pressure, weakness, andallergic reactions.[3] It is unclear if use inpregnancy is safe for the baby.[3] Neostigmine is in thecholinergic family of medications.[3] It works by blocking the action ofacetylcholinesterase and therefore increases the levels ofacetylcholine.[3]
Neostigmine was patented in 1931.[6] It is on theWorld Health Organization's List of Essential Medicines.[7] The term is from Greekneos, meaning "new", and "-stigmine", in reference to the alkaloid,physostigmine, which inspired its design.[8] It is available as ageneric medication.[9]
It is used to improve muscle tone in people withmyasthenia gravis, and also to reverse the effects of non-depolarizingmuscle relaxants such asrocuronium andvecuronium at the end of an operation.[10][11]
Another indication for use is theconservative management of acute colonic pseudo-obstruction, orOgilvie'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 ofenvenomation throughsnakebite.[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]
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 ananti-cholinergic drug such asatropine orglycopyrrolate 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
Acetylcholine is metabolized by the enzymeacetylcholinesterase 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 ofacetylcholinesterase, which blocks theenzyme from breaking down theacetylcholine molecules before they reach thepostsynaptic 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 ofacetylcholine, neostigmine indirectlystimulates bothnicotinic andmuscarinic receptors.[10]
Unlikephysostigmine, neostigmine has a quaternary nitrogen; hence, it is more polar. It does not cross theblood–brain barrier and enter theCNS.[19]
Neostigmine is administered intravenously. The drug should be administered when aperipheral 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]
Neostigmine, which can be viewed as a simplified analog of physostigmine, is made by reacting 3-dimethylaminophenol withN-dimethylcarbamoyl chloride, which forms the dimethylcarbamate, and its subsequent alkylation usingdimethyl sulfate forming the desired compound.
Neostigmine shows notable UV/VIS absorption at 261 nm, 267 nm, and 225 nm.[21]
Neostigmine's1H 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]
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 withN-dimethylcarbamoyl chloride, which forms a dimethylcarbamate. Next, that product is alkylated using dimethyl sulfate, which forms neostigmine.[17]: 103
