Pharmacophore Modeling of Tricyclic Antipsychotics

Psychoses are bipolar disorder characterized by complex mental illness, lack of communication/speech, abnormal thoughts, talks, behavior, and activities, irritation, loss of patience, loss of family touch, negative symptoms such as feelings of sadness, a deficit of attention, and depression. Chlorpromazine is widely available as an antipsychotic drug used in the treatment of psychosis or schizophrenia. Chlorpromazine contains a phenothiazine nucleus having activity against the D2 receptor, but it is not active against the 5HT2A receptor; therefore, it is not used in the treatment of psychoses with depression. Tricyclic antipsychotics including dibenzothiazepine, dibenzodiazepine, and thienobenzodiazepine compounds show very good effects against schizophrenia as well as depression. Pharmacophore modeling of tricyclic antidepressants was established but pharmacophore modeling of tricyclic antipsychotics has not yet been developed. Therefore, an attempt has been made to develop the distance-based pharmacophore followed by the development of quantitative structure-pharmacophore-affinity relationship models for dibenzodiazepine, dibenzothiazepine, thienobenzodiazepines derivatives having affinity against D2 as well as 5HT2A receptors. So, the developed pharmacophore may be fit for both the receptors for further design of the congeneric higher active molecules to be used in depression and psychoses.