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| | Neostigmine Methyl Sulfate Basic information |
| | Neostigmine Methyl Sulfate Chemical Properties |
| Melting point | 175-177 °C(lit.) | | storage temp. | -20°C | | solubility | H2O: 1 g/mL | | form | powder | | color | white | | Water Solubility | 1g/10mL | | Merck | 14,6464 | | InChI | InChI=1S/C12H19N2O2.CH4O4S/c1-13(2)12(15)16-11-8-6-7-10(9-11)14(3,4)5;1-5-6(2,3)4/h6-9H,1-5H3;1H3,(H,2,3,4)/q+1;/p-1 | | InChIKey | OSZNNLWOYWAHSS-UHFFFAOYSA-M | | SMILES | C1(OC(=O)N(C)C)C=CC=C([N+](C)(C)C)C=1.S([O-])(=O)(=O)OC | | CAS DataBase Reference | 51-60-5(CAS DataBase Reference) |
| Hazard Codes | T+ | | Risk Statements | 28-36/37/38-42/43-26/27/28 | | Safety Statements | 36-45-36/37/39-28A | | RIDADR | UN 2811 6.1/PG 2 | | WGK Germany | 3 | | RTECS | CY1225000 | | HazardClass | 6.1(a) | | PackingGroup | II | | HS Code | 29242990 | | Storage Class | 6.1A - Combustible acute toxic Cat. 1 and 2
very toxic hazardous materials | | Hazard Classifications | Acute Tox. 2 Oral
Eye Irrit. 2
Resp. Sens. 1
Skin Irrit. 2
STOT SE 3 | | Toxicity | LD50 in mice (mg/kg): 0.16 i.v.; 0.42 s.c.; 7.5 orally, (Randall, Lehmann) |
| | Neostigmine Methyl Sulfate Usage And Synthesis |
| Description | Neostigmine is a reversible inhibitor of acetylcholinesterase (AChE; Kd = 260 μM). In a rat model of knee joint inflammation, intrathecal administration of neostigmine (2-30 μg) increases endogenous acetylcholine levels and dose-dependently increases the latency of paw withdrawal in response to thermal and mechanical stimuli (ED50s = 6.6 and 3.5 μg, respectively). Neostigmine (5 μg, i.p.) restores muscle action potentials in mice with a thymopoietin-induced neuromuscular block. Formulations containing neostigmine have been used in the treatment of myasthenia gravis and Ogilvie syndrome. | | Chemical Properties | Crystalline Solid | | Uses | Cholinergic; miotic; antidote (curare) | | Definition | ChEBI: Neostigmine methyl sulfate is an arylammonium sulfate salt. It has a role as an EC 3.1.1.8 (cholinesterase) inhibitor. | | Brand name | Prostigmine (ICN). | | General Description | Neostigmine methylsulfate,(m-hydroxyphenyl)trimethylammonium methylsulfatedimethylcarbamate or the dimethylcarbamic ester of 3-hydroxyphenyltrimethylammoniummethylsulfate (Prostigminmethylsulfate), is a bitter, odorless, white, crystalline powder.It is very soluble in water and soluble in alcohol. Solutionsare stable and can be sterilized by boiling. The compound istoo hygroscopic for use in a solid form and thus is alwaysused as an injection. Aqueous solutions are neutral to litmus. | | Clinical Use | The methylsulfate salt is used postoperatively as a urinarystimulant and in the diagnosis and treatment of myastheniagravis. | | Synthesis | Example 9 Preparation of neostigmine methyl sulfate (general procedure)
To a 250 mL four-necked round-bottomed flask was added 3-(dimethylamino)phenyldimethylcarbamate and acetone obtained in Example 1. Dimethyl sulfate (1.66 eq.) was added dropwise to the flask at room temperature. The reaction mixture was stirred overnight and then cooled to 5 °C to 10 °C and kept for 2 hours. This was followed by filtration and the filtrate was washed with isopropanol. The residue was dried under vacuum at room temperature to give the crude product neostigmine methyl sulfate. Purification was carried out by recrystallization from isopropanol.
Yield: 85%.
Properties: light yellow oil
HPLC Purity: 99.21%. | | Purification Methods | Crystallise the sulfate from EtOH or Me2CO (m 143-144o). Its solubility in H2O is ~10%. [Beilstein 13 III 939.] (It is cholinergic and highly TOXIC.) | | References | [1] Patent: WO2012/131699, 2012, A1. Location in patent: Page/Page column 15
[2] Pharmazie, 2001, vol. 56, # 2, p. 181 - 182
[3] Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation), 1941, vol. 14, p. 524,526
[4] Chem.Abstr., 1942, p. 3159
[5] Patent: CH208883, 1938, |
| | Neostigmine Methyl Sulfate Preparation Products And Raw materials |
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