Partial Dopamine Receptor Agonists as Newer Atypical Antipsychotics:Intrinsic Activity Appropriate for Treatment of Schizophrenic Patients

Yuji      Odagaki

Abstract

Conventional antipsychotic drugs, which have been used for a half century to treat a range of major psychiatric disorders like schizophrenia, are being replaced by modern “atypical antipsychotics”. Although the term “atypical” has been applied broadly to antipsychotic drugs marketed in the past decade, these newer drugs are strikingly heterogeneous in chemical, pharmacological, and clinical points of view. Recently, much attention has been directed to partial dopamine receptor agonists as promising atypical antipsychotics with properties of “dopamine system stabilizers”, which behave either as agonists or antagonists depending on the functional state of the dopamine receptors. Aripiprazole (OPC-14597) is the first and unique antipsychotic drug with such pharmacological properties commercially available in US, Europe, and most recently in Japan. In the present article, the term “atypicality” is critically revisited, and the place of partial dopamine receptor agonists in atypical antipsychotics is overviewed with special reference to the intrinsic activities appropriate for treating the schizophrenic patients with greatest efficacy and least liability of adverse effects such as extrapyramidal symptoms.

Keywords: Atypical antipsychotics, aripiprazole, dopamine receptor, partial agonist, intrinsic activity, presynaptic autoreceptor, schizophrenia, dopamine system stabilizer