Mesoridazine

Legal statusLegal status Pharmacokinetic dataProtein binding4%MetabolismHepatic/renalElimination half-life24 to 48 hoursExcretionBiliary and renalIdentifiersCAS NumberPubChem CIDIUPHAR/BPSDrugBankChemSpiderUNIIKEGGChEBIChEMBLCompTox Dashboard (EPA)Chemical and physical dataFormulaC₂₁H₂₆N₂OS₂Molar mass386.57 g·mol⁻¹3D model (JSmol)Melting point130 °C (266 °F)Solubility in waterinsoluble mg/mL (20 °C)  (verify)

Mesoridazine (Serentil) is a phenothiazine class drug that is used in the treatment of schizophrenia.^[2] It is one of the active metabolites 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Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram.^[3]

It currently appears to be unavailable worldwide.

Synthesis

2-Methylthiophenothiazine [7643-08-5] (1) is treated with acetic anhydride] to give the protected amide, ie 10-acetyl-2-methylthiophenothiazine, CID:69367526. Oxidation of this by means of hydrogen peroxide and removal of the acetyl protecting group with potassium carbonate in methanol solution gives 2-methylsulfonylphenothiazine [23503-68-6] (3). Introduction of the sidechain by alkylation with 2-(2-chlorethyl)-1-methylpiperidine [50846-01-0] (6) in the presence of sodamide, afforded the desired mesoridazine (5).

References