Mesoridazine (Serentil) is a

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. ...

class drug that is used in the treatment of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. It is one of the active metabolites 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 The branded product was withdrawn worldwid ...

. 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 (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

tardive dyskinesia Tardive dyskinesia (TD) is an iatrogenic disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips, which occurs following treatment with medication. Additional mo ...

and the potentially fatal

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...

. Mesoridazine was withdrawn from the United States market in 2004 due to dangerous side effects, namely irregular heart beat and QT-prolongation of the electrocardiogram. Mesoridazine is on the FDA's Discontinued Drug Product List.

Synthesis

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

acetic anhydride Acetic anhydride, or ethanoic anhydride, is the chemical compound with the chemical formula, formula . Commonly abbreviated , it is one the simplest organic acid anhydride, anhydrides of a carboxylic acid and is widely used in the production of c ...

] 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

{{Tricyclics M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Phenothiazines Piperidines Sulfoxides Tertiary amines Typical antipsychotics Withdrawn drugs