Mesoridazine

Mesoridazine

Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a682306
Routes of administration	oral, intravenous
ATC code	N05AC03 (WHO)
Legal status
Legal status	In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding	4%
Metabolism	Hepatic/Renal
Elimination half-life	24 to 48 hours
Excretion	Biliary and renal
Identifiers
IUPAC name 10-{2-[(RS)1-Methylpiperidin-2-yl]ethyl}- 2-methylsulfinyl- 10H-phenothiazine
CAS Number	5588-33-0 Y
PubChem CID	4078
DrugBank	DB00933 N
ChemSpider	3936 Y
UNII	5XE4NWM740
KEGG	D02671 Y
ChEBI	CHEBI:6780 Y
ChEMBL	ChEMBL1088 Y
CompTox Dashboard (EPA)	DTXSID3023265
Chemical and physical data
Formula	C21H26N2OS2
Molar mass	386.576 g/mol g·mol−1
3D model (JSmol)	Interactive image
Melting point	130 °C (266 °F)
Solubility in water	insoluble mg/mL (20 °C)
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
NY (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 name is partially derived from the MEthyl-SulfOxy group in the 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Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.

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).