Quetiapine, structure

Structurally quetiapine is related to clozapine and olanzapine. Quetiapine has high affinity for 5-HT2A receptors and lower... 

Receptor-Binding Studies. Quetiapine (Seroquel) is also a dibenzothiazepine derivative produced by altering the structure of clozapine. This agent has an affinity for multiple brain receptors, a low propensity to evoke EPS in preclinical tests considered predictive of antipsychotic activity, and does not produce sustained plasma prolactin levels. 

FIGURE 11—36. Structural formulas for clozapine and four other antipsychotics, namely, olanzapine, quetiapine, loxapine, and zotepine. Interestingly, all five of these are also SDAs, but not all of them appear to be atypical antipsychotics (e.g., loxapine is conventional, and zotepine is still being characterized). Abo, clinical properties and pharmacological characteristics vary considerably among those that are clearly atypical (i.e., clozapine, olanzapine, and quetiapine). 

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. 

Because of the apparent structural similarities of these clozapine-analogues, the question arises of how different are these compounds in their receptorial, pharmacological, and clinical actions Some of the major features of the clozapine analogues, olanzapine and quetiapine, are compared with clozapine in the following section. 

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. 

Drug discrimination has also been used to compare antipsychotic drugs that act through different receptor mechanisms. The close structural analogs olanzapine and quetiapine... 

Several newer drugs of varied beterocyclic structure are also effeetive in schizophrenia, ineluding elozapine, loxapine, olanzapine, molindone, pimozide, risperidone, quetiapine, and sertindole. In some cases, these atypical antipsychotic drugs have proved to be more effective and less toxic than the older drugs. However, they are much more eostly than standard drugs, most of whieh are preseribed generically. 

Quetiapine, marketed as Seroquel, is a heavily prescribed antipsychotic drug used in the treatment of schizophrenia and bipolar disorder. Convert the following representation into a skeletal structure, and give the molecular formula of quetiapine. 

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