101-26-8

Basic information

• Product Name: Mestinon
• Synonyms: PYRIDOSTIGMINE BROMIDE;PYBR;1-methyl-3-hydroxypyridiniumbromidedimethylcarbamate;3-(((dimethylamino)carbonyl)oxy)-1-methyl-pyridiniubromide;3-(dimethylcarbamyloxy)-1-methylpyridiniumbromide;3-hydroxy-1-methylpyridiniumbromidedimethylcarbamate;3-hydroxy-1-methylpyridiniumbromidedimethylcarbamate(ester);dimethylcarbamicacidesterof3-hydroxy-1-methylpyridiniumbromide
• CAS NO: 101-26-8
• Molecular Formula: Br*C₉H₁₃N₂O₂
• Molecular Weight: 261.12
• EINECS: 202-929-9
• Product Categories: Pyridinium Compounds;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Pharmaceutical raw material;API;MESTINON
• Mol File: 101-26-8.mol
• Article Data: 1

Chemical Properties

• Melting Point: 154 °C
• Boiling Point: 88 (25 torr)
• Appearance: Pale yellow to colorless liquid
• Density: 0.9613 g/cm3 (20oC)
• Storage Temp.: Refrigerator
• Solubility: Very soluble in water and in ethanol (96 per cent).
• Merck: 14,7977
• CAS DataBase Reference: Mestinon(CAS DataBase Reference)
• NIST Chemistry Reference: Mestinon(101-26-8)
• EPA Substance Registry System: Mestinon(101-26-8)

Safety Data

• Hazard Codes: T+
• Statements: 26/27/28-43
• Safety Statements: 22-36/37/39-45
• RIDADR: UN 2811 6.1/PG 2
• WGK Germany: 3
• RTECS: UU5270000
• HazardClass: 6.1
• PackingGroup: II
• Hazardous Substances Data: 101-26-8(Hazardous Substances Data)

Usage

Description

Pyridostigmine is an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE; IC50s = 0.35 and 1 μM, respectively, for the human enzymes). Pyridostigmine (10 μM) reduces decreases in AChE activity induced by the organophosphate pesticides diisopropyl fluorophosphate, chlorpyrifos-oxon, diazinon-oxon, paraoxon, and malaoxon in isolated bovine red blood cells. It also reduces soman-induced membrane depolarization and decreases in AChE activity in isolated human muscle bundles in a concentration-dependent manner. Pyridostigmine (3 mg/kg per day for four weeks) prevents tachycardia and increases in sympathetic tone in mice following myocardial infarction induced by left coronary artery ligation. Formulations containing pyridostigmine have been used in the treatment of myasthenia gravis and as neuromuscular protective agents against organophosphate poisoning.

Chemical Properties

White Solid

Uses

Cholinergic, used in the treatment of myasthenia gravis, and is a pre-exposure antidote to chemical warfare agents.

Brand name

Mestinon (Valeant); Regonol (Sandoz).

General Description

Pyridostigmine bromide,3-hydroxy-1-methylpyridinium bromide dimethylcarbamateor pyridostigmine bromide (Mestinon), occurs as a white, hygroscopic,crystalline powder with an agreeable, characteristicodor. It is freely soluble in water, alcohol, and chloroform.Pyridostigmine bromide is about one fifth as toxic asneostigmine. It appears to function in a manner similar tothat of neostigmine and is the most widely used anticholinesteraseagent for treating myasthenia gravis. Theliver enzymes and plasma cholinesterase metabolize thedrug. The principal metabolite is 3-hydroxy-N-methylpyridinium.Orally administered pyridostigmine has a half-lifeof 90 minutes and a duration of action of between 3 and6 hours.

Biochem/physiol Actions

Acetylcholinesterase inhibitor.

Clinical Use

Myasthenia gravis

Drug interactions

Potentially hazardous interactions with other drugs Aminoglycosides, clindamycin and polymyxins antagonise effects of pyridostigmine.

Metabolism

Pyridostigmine undergoes hydrolysis by cholinesterases and is also metabolised in the liver. It appears that 75% of the plasma clearance of pyridostigmine depends on renal function. 3-Hydroxy-N-methylpyridinium has been identified as one of the 3 metabolites isolated from the urine. Pyridostigmine is excreted mainly in the urine as unchanged drug and metabolites.

InChI:InChI=1/C9H13N2O2.BrH/c1-10(2)9(12)13-8-5-4-6-11(3)7-8;/h4-7H,1-3H3;1H/q+1;/p-1

Synthetic route

methyl bromide (74-83-9) + 3-(N,N-Dimethylcarbamoyl)-oxipyridin (51581-32-9) → pyridostigmine bromide (101-26-8)

Conditions	Yield
In acetone for 48h; Ambient temperature;	89%
With benzene
With toluene
With acetone
With acetone

3-HYDROXYPYRIDINE (109-00-2) → pyridostigmine bromide (101-26-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 47 percent / Et3N / toluene / 4 h / Heating 2: 89 percent / acetone / 48 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: triethylamine; benzene 2: toluene View Scheme
Multi-step reaction with 2 steps 1: chloroform / Behandeln des Reaktionsprodukts mit wss.Dimethylamin-Loesung 2: acetone View Scheme
Multi-step reaction with 2 steps 1: xylene 2: acetone View Scheme

pyridostigmine bromide (101-26-8) → 1-methyl-3-hydroxypiperidine (3554-74-3) + 1-methyl-3-piperidone (5519-50-6) + Dimethyl-carbamic acid 1-methyl-1,2,3,6-tetrahydro-pyridin-3-yl ester + 3-<(N,N-dimethyl)-carbamoyl>-1-methyl-1,2,5,6-tetrahydropyridine + 3-dimethylcarbamoyloxy-1-methyl-piperidine (6659-30-9)

Conditions	Yield
With sodium tetrahydroborate Product distribution; different pH, temperature, time and solvents;

pyridostigmine bromide (101-26-8) → Dimethyl-carbamic acid 1-methyl-1,2,3,6-tetrahydro-pyridin-3-yl ester + 3-<(N,N-dimethyl)-carbamoyl>-1-methyl-1,2,5,6-tetrahydropyridine + 3-dimethylcarbamoyloxy-1-methyl-piperidine (6659-30-9)

Conditions	Yield
With sodium tetrahydroborate In water for 15h; Ambient temperature;
With sodium tetrahydroborate In water for 0.25h; Ambient temperature;

C62H68N16O24S4(4-)*4Na(1+) + pyridostigmine bromide (101-26-8) → C9H13N2O2(1+)*Br(1-)*C62H68N16O24S4(4-)*4Na(1+)

Conditions	Yield
In aq. phosphate buffer pH=7.4; UV-irradiation;

Upstream product

• 74-83-9 methyl bromide 
• 51581-32-9 3-(N,N-Dimethylcarbamoyl)-oxipyridin 
• 109-00-2 3-HYDROXYPYRIDINE 

Downstream Products

• 6659-30-9 3-dimethylcarbamoyloxy-1-methyl-piperidine 
• 3554-74-3 3-Hydroxy-1-methylpiperidine 
• 5519-50-6 1-methyl-3-piperidone 

Relevant articles and documents

Determination of the Structure of Products of the Reduction of Pyridostigmine with NaBH4

The chemical structure of 5 different products of pyridostigmine obtained by reduction with NaBH4 was determined by GC - MS and subsequently confirmed by means of 1H and 13C NMR spectroscopy.Reaction conditions leading almost exclusively to the main product: 3--1-methyl-1,2,5,6-tetrahydropyridine (4) have been determined. - Key words: Pyridostigmine, 3--1-methylpyridiniumbromide, Reduction Products, 1H NMR Spectra, 13C NMR Spectra