Mesoridazine (Serentil) is a

piperidine Piperidine is an organic compound with the molecular formula (CH2)5NH. This heterocyclic compound, heterocyclic amine consists of a six-membered ring containing five methylene bridges (–CH2–) and one amine bridge (–NH–). It is a colorless ...

neuroleptic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...

drug belonging to the class of drugs called

phenothiazine Phenothiazine, abbreviated PTZ, is an organic compound that has the formula S(C6H4)2NH and is related to the thiazine-class of heterocyclic compounds. Derivatives of phenothiazine are highly bioactive and have widespread use and rich history. T ...

s, used in the treatment of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...

. It is a metabolite of

thioridazine Thioridazine (Mellaril or Melleril) is a first generation antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis. The branded product was withdrawn worldwide ...

. 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 Akathisia is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and an inability to sit still. Usually, the legs are most prominently affected. Those affected may fidget, rock back and ...

tardive dyskinesia Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movemen ...

and the potentially fatal

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to neuroleptic or antipsychotic medication. Symptoms include high fever, confusion, rigid muscles, variable blood pressure, sweating, and fas ...

. 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. It currently appears to be unavailable worldwide.

Synthesis

2-Methylthiophenothiazine 643-08-5(1) is treated with

acetic anhydride Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula (CH3CO)2O. Commonly abbreviated Ac2O, it is the simplest isolable anhydride of a carboxylic acid and is widely used as a reagent in organic synthesis. It is a col ...

] 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 3503-68-6(3). Introduction of the sidechain by alkylation with 2-(2-chlorethyl)-1-methylpiperidine 0846-01-0(6) in the presence of sodamide, afforded the desired mesoridazine (5).

References

Muscarinic antagonists Phenothiazines Piperidines Sulfoxides Tertiary amines Typical antipsychotics Withdrawn drugs {{nervous-system-drug-stub