Unique Pharmacological Profile of a Novel Antipsychotic Drug, Aripiprazole (OPC‐14597)

Aripiprazole (OPC-14597) is a novel antipsychotic agent with an unusual pharmacological profile that is atypical of compounds affecting the dopaminergic system. This agent is a quinolinone derivative related to OPC-4392 (Fig. 1). OPC-4392 acts on dopamine (DA) neurons and their nerve terminals as an autoreceptor agonist, eliciting inhibitory effects on ventral tegmental and nigral DA neurons (14,20). OPC-4392 has no postsynaptic DA receptor blocking activities (20). In clinical trials OPC-4392 improved the negative and the positive symptoms of chronic schizophrenic patients, such as hallucination, delusion, and psychiatric excitement. Similar effects on negative symptoms were observed with other DA autoreceptor agonists, such as EMD 49980, talipexole and terguride (8,20,17). Further attempts to develop a useful antipsychotic drug that displays both presynaptic DA agonistic and postsynaptic DA antagonistic activities and improves negative as well as positive symptoms in schizophrenic patients resulted in the discovery of aripiprazole. An early phase 11 clinical study on aripiprazole was recently performed in 56 schizophrenic patients by M. Toru et al. in Japan (24). According to the assessment by BPRS in this study, significant global improvement of negative symptoms (emotional withdrawal, motor retardation, blunted affect) and positive signs (suspiciousness, unusual thoughts, hallucinatory behaviors) was achieved. Negligible side effects, including mild extrapyramidal symptoms, were encountered. Aripiprazole may be considered a useful antipsychotic agent with a unique pharmacological profile.