Mesoridazine

Mesoridazine

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 Y
ATC code	N05AC03
PubChem	CID 4078
DrugBank	DB00933
ChemSpider	3936 Y
UNII	5XE4NWM740 Y
KEGG	D02671 Y
ChEBI	CHEBI:6780 Y
ChEMBL	CHEMBL1088 Y
Chemical data
Formula	C21H26N2OS2
Mol. mass	386.576 g/mol
SMILES O=S(c2cc1N(c3c(Sc1cc2)cccc3)CCC4N(C)CCCC4)C
InChI InChI=1S/C21H26N2OS2/c1-22-13-6-5-7-16(22)12-14-23-18-8-3-4-9-20(18)25-21-11-10-17(26(2)24)15-19(21)23/h3-4,8-11,15-16H,5-7,12-14H2,1-2H3 Y Key:SLVMESMUVMCQIY-UHFFFAOYSA-N Y
Physical data
Melt. point	130 °C (266 °F)
Solubility in water	insoluble mg/mL (20 °C)
Y (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Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.^[1]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

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

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.

• J. Renz, G. Schwarb, U.S. Patent 3,084,161 (1960).

References