Mesoridazine

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Mesoridazine
Mesoridazine.png
Mesoridazine3Dan2.gif
Systematic (IUPAC) name
10-{2-[(RS)1-Methylpiperidin-2-yl]ethyl}- 2-methylsulfinyl- 10H-phenothiazine
Clinical data
Trade names Serentil
AHFS/Drugs.com Micromedex Detailed Consumer Information
MedlinePlus a682306
Pregnancy cat. C (US)
Legal status Prescription only
Routes oral, intravenous
Pharmacokinetic data
Protein binding 4%
Metabolism Hepatic/Renal
Half-life 24 to 48 hours
Excretion Biliary and renal
Identifiers
CAS number 5588-33-0 YesY
ATC code N05AC03
PubChem CID 4078
DrugBank DB00933
ChemSpider 3936 YesY
UNII 5XE4NWM740 YesY
KEGG D02671 YesY
ChEBI CHEBI:6780 YesY
ChEMBL CHEMBL1088 YesY
Chemical data
Formula C21H26N2OS2 
Mol. mass 386.576 g/mol
Physical data
Melt. point 130 °C (266 °F)
Solubility in water insoluble mg/mL (20 °C)
 YesY (what is this?)  (verify)

Mesoridazine (Serentil) is a piperidine neuroleptic drug belonging to the class of drugs called phenothiazines, used in the treatment of schizophrenia. It is a metabolite of thioridazine. The drug's name is derived from the methylsulfoxy and piperidine functional groups in its chemical structure.

It has central antiadrenergic, antidopaminergic, antiserotonergic and weak muscarinic anticholinergic effects.

Serious side effects include akathisia, tardive dyskinesia and the potentially fatal neuroleptic malignant syndrome.

Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.[1]

It currently appears to be unavailable worldwide.

Chemistry[edit]

Mesoridazine (10-[2-(1-methyl-2-piperidyl)ethyl]-2-(methylsufinyl)phenothiazine) is synthesized by an analogous scheme to that seen already for thioridazine.

Mesoridazine synthesis:[2] J. Renz, G. Schwarb, U.S. Patent 3,084,161 (1960).

However, it is also synthesized by alkylating the acidic form of 2-methylthiophenothiazine -methylsulfonylphenothiazine- using 2-(2-chloroethyl)-1-methylpiperidine. 2-methylthiophenothiazine is initially acylated at the nitrogen atom using acetic anhydride, giving 10-acetyl-2-methylthiophenothiazine. The resulting acetyl derivative is further oxidized by hydrogen peroxide into 10-acetyl-2-methylsulfonylpenothiazine. Deacylation of this product in potassium carbonate methanol solution gives 2-methylsulfanylphenothiazine, which is alkylated by 2-(2-chlorethyl)-1-methylpiperidine in the presence of sodamide, affording the desired mesoridazine.

References[edit]

  1. ^ [1]
  2. ^ Bourquin, J. -P.; Schwarb, G.; Gamboni, G.; Fischer, R.; Ruesch, L.; Guldimann, S.; Theus, V.; Schenker, E.; Renz, J. (1958). "Synthesen auf dem Phenothiazin-Gebiet. 2. Mitteilung. N-substituierte Mercaptophenothiazin-Derivate". Helvetica Chimica Acta 41 (4): 1072. doi:10.1002/hlca.19580410420.  edit