Clozapine chemical structure

Recently a number of novel, non-classical chemical structures, referred to as atypical neuroleptics, have been described clozapine (4.93), risperidone (4.94), olanzapine (4.95), and sertindole (4.96). These atypical neuroleptics have two distinguishing... 

Clozapine is considered to be the prototype of the atypical antipsychotics, as it was the first to be recognized as having few if any extrapyramidal side effects, not causing tardive dyskinesia, and not elevating prolactin. Clozapine is one of five antipsychotics with somewhat related chemical structures (Fig. 11-36). Although certainly a serotonin 2A-dopamine 2 antagonist, clozapine also has one of the most complex... 

This agent has a different chemical structure (Fig. 11—38) and a considerably simpler pharmacologic profile than clozapine (Fig. 11—39). Risperidone is especially atypical at lower doses but can become more conventional at high doses in that EPS can occur if the dose is too high. Risperidone thus has favored uses, not only in schizophrenia at moderate doses but also for conditions in which low doses of conventional antipsychotics have been used in the past, for example, for elderly patients with... 

Although olanzapine has a chemical structure related to that of clozapine (Fig. 11 — 36), it is more potent than clozapine and has several differentiating pharmacologic... 

Quetiapine also has a chemical structure related to that of clozapine (Fig. 11—36), but it has several differentiating pharmacologic (Fig. 11—41) and clinical features, not only as compared with clozapine (Fig. 11—37) but also as compared with risperidone (Fig. 11-39) and olanzapine (Fig. 11-40). Quetiapine is very atypical in that it causes virtually no EPS at any dose and no prolactin elevations. Thus, quetiapine tends to be the preferred atypical antipsychotic for patients with Parkinson s disease and psychosis. It is also useful in schizophrenia, bipolar disorder, and other types of psychosis, in which it has few extrapyramidal side effects. 

Fig. 13.1 Chemical structure of clozapine, some of its structural analogues, typical (chlorpromazine, haloperidol) and atypical antipsychotics (risperidone, ziprasidone, sertindole and amisulpride) unrelated to clozapine.

Chart 1.10 Chemical structures of clozapine (23), risperidone (24), olanzapine (25), seroquel (26). 

The discovery of the atypical antipsychotic clozapine opened a new era and set new standards in the drug treatment of schizophrenia. Modifications of the diben-zoazepine structure in clozapine resulted in olanzapine and quetiapine, which are among the most frequently used antipsychotic drugs. From a chemical viewpoint, clozapine, olanzapine and quetiapine can be considered as structural analogues. Although they share some common features in their molecular mechanism of action, the three compounds show significant differences in their clinical efficacy and adverse event profile. 

FIGURE 15.10 Product ion spectra and proposed structures of clozapine adducts formed in rat liver microsome incubation with (a) NAC and (b) GSH. (a) Positive product ion spectra acquired by negative NL-directed EPI with polarity switch, (b) Positive product ion spectra acquired by negative Pl-directed EPI with polarity switch. [Reprinted from Jian et al. (2009) with permission of American Chemical Society.]... 

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