Comparison of the anti-dopamine D2and anti-serotonin 5-HT2Aactivities of chlorpromazine, bromperidol, haloperidol and second-generation antipsychotics parent compounds and metabolites thereof

Authors:
Publisher website
Google Scholar
Abstract
Second-generation antipsychotics, which have become the standard drug therapies for schizophrenia, are known to have a serotonin 5-HT2Areceptor blocking effect in addition to a dopamine D2receptor blocking effect. However, although chlorpromazine (CPZ) has a 5-HT2Areceptor blocking effect and has the profile of a second-generation antipsychotic in vitro, it loses this pharmacological profile in vivo. In order to elucidate the differences between the in vivo and in vitro pharmacological characteristics of CPZ, we used a radioreceptor assay to measure the anti-D2activity and the anti-5-HT2Aactivity of CPZ and five major metabolites of CPZ, and compared the results to the anti-D2activity and anti-5-HT2Aactivity of risperidone, zotepine, perospirone, the major metabolites of each of these drugs, and olanzapine, bromperidol, and haloperidol. The subjects were 182 patients who had received diagnoses of schizophrenia based on the DSM-IV criteria. The results revealed that CPZ exhibited little anti-5-HT2Aactivity, regardless of the anti-D2activity level, and that none of the metabolites possessed anti-5-HT2Aactivity. However, both the parent compounds and the metabolites of each of the second-generation antipsychotics possessed both anti-D2activity and anti-5-HT2Aactivity. This clarified that, unlike second-generation antipsychotics, the reason CPZ loses its second-generation antipsychotic profiles in vivo is because it does not have any metabolites that possess anti-5-HT2Aactivity.

This publication has 16 references indexed in Scilit: