Mianserin hydrochloride

Mianserin hydrochloride Basic information
Product Name:Mianserin hydrochloride
Synonyms:1,2,3,4,10,14BETA-HEXAHYDRO-2-METHYL-DIBENZO-[C,F]PYRAZINO[1,2-A]AZEPINE HYDROCHLORIDE;1,2,3,4,10,14B-HEXAHYDRO-2-METHYL-DIBENZO[C,F]PYRAZINO[1,2-A]AZEPINE HYDROCHLORIDE;1,2,3,4,10,14b-hexahydro-2-methyldibenzo(c,f)pyrazino(1,2-a)azepinehydrochlo;MIANSERINE HCL;MIANSERINE HYDROCHLORIDE;MIANSERIN HCL;MIANSERIN HYDROCHLORIDE;MIANSERIN HYDROCHLORIDE SEROTONIN ANTAGO NIST
CAS:21535-47-7
MF:C18H21ClN2
MW:300.83
EINECS:244-426-7
Product Categories:Inhibitors;ATHYMIL;Serotonin receptor;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
Mol File:21535-47-7.mol
Mianserin hydrochloride Structure
Mianserin hydrochloride Chemical Properties
Melting point >230oC (dec.)
Fp 9℃
storage temp. 2-8°C
solubility H2O: 3.4 mg/mL
form neat
color Off-White to Pale Yellow
Water Solubility Soluble in water, ethanol, methanol, and dimethylformamide.
Merck 14,6172
InChIKeyYNPFMWCWRVTGKJ-UHFFFAOYSA-N
CAS DataBase Reference21535-47-7(CAS DataBase Reference)
Safety Information
Hazard Codes Xn,Xi,T,F
Risk Statements 22-39/23/24/25-23/24/25-11
Safety Statements 7-16-36/37-45
RIDADR 3249
WGK Germany 3
RTECS HP8780000
HS Code 2933.59.8000
HazardClass 6.1(b)
PackingGroup III
ToxicityLD50 in male, female mice (mg/kg): 365, 390 orally; 32.5, 31.0 i.v. (van Riezen)
MSDS Information
ProviderLanguage
SigmaAldrich English
Mianserin hydrochloride Usage And Synthesis
Chemical PropertiesOff-White Solid
OriginatorTolvin,Organon,W. Germany,1975
UsesMianserin hydrochloride is a tetracyclic antidepressant with an EEG and clinical activity profile similar to amitriptyline. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors.
UsesMianserin hydrochloride is used as an antidepressant, antagonist, inverse agonist at 5-HT2 serotonin receptors, also blocks the H1 histamine receptor and the α2 adrenoceptor.
Manufacturing Process(A) 25 g of 2-benzylaniline dissolved in 150 ml of benzene are cooled down in an ice bath to 8°C. To this solution are added 15 ml of pyridine and after that a solution of 15 ml of chloroacetyl chloride in 25 ml of benzene, maintaining the temperature of the reaction mixture at 10° to 15°C. After stirring for 1 hour at room temperature 25 ml of water are added and the mixture is shaken for 30 minutes. Next the mixture is sucked off and the benzene layer separated. Then the benzene layer is washed successively with 2 N HCl, a sodium carbonate solution and water. The extract dried on sodium sulfate is evaporated and the residue crystallized together with the crystals obtained already from benzene. Yield 18 g; MP 130° to 133°C.
(B) 40 g of N-chloroacetyl-2-benzylaniline are heated for 2 hours at 120°C together with 50 ml of phosphorus oxychloride and 320 g of polyphosphoric acid. Next the reaction mixture is poured on ice and extracted with benzene. The extract is washed and dried on sodium sulfate and the benzene distilled off. The product obtained (31g) yields after recrystallization 24 g of 6- chloromethyl-morphanthridine of MP 136° to 137°C.
(C) 10 g of 6-chloromethyl-morphanthridine are passed into 150 ml of a solution of methylamine in benzene (10%). After storage of the solution for 20 hours at 0° to 5°C the methylamine hydrochloride formed is sucked off and the filtrate evaporated to dryness. There remains as residue 11 g of crude 6-methylaminomethyl-morphanthridine.
(D) 11 g of crude 6-methylaminomethyl-morphanthridine are dissolved in 50 ml of absolute ether. While cooling in ice 2.7 g of lithium aluminumhydride, dissolved in 100 ml of absolute ether, are added. After boiling for 1 hour and cooling down in ice 11 ml of water are added slowly dropwise while stirring. After stirring for another 30 minutes at room temperature the mixture is sucked off and the filtrate evaporated to obtain 11 g of crude 5,6-dihydro-6- methylaminomethyl-morphanthridine in the form of a light yellow oil.
(E) 10 g of 5,6-dihydro-6-methylaminomethyl-morphanthridine are heated slowly, in 30 minutes, from 100° to 160°C with 7 g of pure diethyloxalate and after that from 160° to 180°C in 45 minutes. After cooling down the reaction mixture is stirred with benzene. The crystals are sucked off and yield after crystallization from dimethylformamide 9 g of 1,2-diketo-3(N)-methyl- 2,3,4,4a-tetrahydro-1H-pyrazino-[1,2-f]-morphanthridine of MP 245° to 247°C.
(F) 9 g of the diketo-pyrazino-morphanthridine compound obtained above are reduced with diborane to give mianserin.




Therapeutic FunctionSerotonin antagonist, Antihistaminic
Biological ActivityMianserin hydrochloride is a non-selective 5-HT2 receptor antagonist (Ki values are 0.0080 and 0.0081 μM for human 5-HT2A and 5-HT2C receptors expressed in HEK293 cells respectively). Has moderate affinity for 5-HT6. Antidepressant.
Clinical UseAntidepressant
Drug interactionsPotentially hazardous interactions with other drugs
Alcohol: increased sedative effect.
Antibacterials: avoid with linezolid and tedizolid. Antidepressants: avoid with MAOIs and moclobemide.
Antiepileptics: convulsive threshold possibly lowered; concentration reduced by carbamazepine, fosphenytoin, phenobarbital, phenytoin and primidone.
Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.
Safinamide: increased risk of hypertension and CNS excitation.



MetabolismMianserin is hepatically metabolised via aromatic hydroxylation, N-oxidation and N-demethylation. There are 3 urinary metabolites, (N-desmethyl, 8-hydroxy, and N-oxide derivative) which have been identified. The desmethyl metabolite, which is also active, has similar pharmacokinetic behaviour as the parent compound. Mianserin is excreted in the urine, almost entirely as its metabolites, either free or in conjugated form; 14-28% in the faeces.
storageRoom temperature
Mianserin hydrochloride Preparation Products And Raw materials
Raw materialsLithium Aluminum Hydride-->2-Aminobenzyl alcohol-->Formaldehyde-->Styrene oxide-->Monoethanolamine
desmethylmianserin Methylparaben Methyl Bensulfuron methyl (2-AMINO-2-PHENYLETHYL)DIMETHYLAMINE Parathion-methyl Topotecan hydrochloride Mianserin hydrochloride Cetirizine hydrochloride Tetramethylpyrazine MIANSERIN 1-AdaMantanethylaMine Thiophanate-methyl Diphenhydramine Hydrochloride Sulfachoropyrazine sodium Methyl acetate Methyl bromide METSULFURON METHYL

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