Clotiapine

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Clotiapine (Entumine) is an atypical antipsychotic of the dibenzothiazepine chemical class. It was first introduced in a few European countries (namely, Belgium, Italy, Spain and Switzerland), Argentina, Taiwan and Israel in 1970.

Some sources regard clotiapine as a typical antipsychotic rather than atypical due to its high incidence of extrapyramidal side effects compared to the atypicals like clozapine and quetiapine, to which it is structurally related.Despite its profile of a relatively high incidence of extrapyramidal side effects it has demonstrated efficacy in treatment-resistant schizophrenic patients according to a number of psychiatrists with clinical experience with it, some weak clinical evidence supports this view too.

Ullmann condensation of the substituted thiosalyciclic acid with ortho-chloronitrobenzene results in the displacement of chlorine by thiophenoxide and the formation of the thioether . The nitro group in this last intermediate is then reduced to an aniline ; the resulting amino acid is then cyclized thermally to the lactam . Treatment of that with phosphorus oxychloride gives the imino chloride. Reaction with N-methylpiperazine leads to the replacement of chlorine by nitrogen and the formation of clothiapine .