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

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

Uses

Used in Pharmaceutical Industry:
Mestinon is used as a cholinergic agent for the treatment of myasthenia gravis. It helps in modulating the activity of acetylcholinesterase and butyrylcholinesterase, which are essential for the proper functioning of the nervous system.
Used in Pre-Exposure Antidote:
Mestinon is used as a pre-exposure antidote to chemical warfare agents, particularly organophosphate poisoning. It helps in reducing the effects of these toxic substances on the nervous system by inhibiting the activity of acetylcholinesterase and butyrylcholinesterase.
Used in Neuromuscular Protection:
Mestinon is used as a neuromuscular protective agent against organophosphate poisoning. It prevents tachycardia and increases in sympathetic tone in mice following myocardial infarction induced by left coronary artery ligation.
Brand Names:
Mestinon (Valeant); Regonol (Sandoz).

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

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

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