Phase 1 study of a new antipsychotic drug, OPC-4392

Abstract

1. 1. A phase I study of OPC-4392 (OPC), a quinolinone derivative recently developed in Japan and recognized to have an agonistic effect on dopamine autoreceptors, was performed in 7 male healthy volunteers in comparison with chlorpromazine (CPZ). 2. 2. Clinical pharmacology The main clinical symptoms of OPC were sleepiness, weakness, fatigability, heavy headedness, disturbance of concentration, nausea, etc. The severity of these symptoms increased dose-dependently, and the upper limit dosage of OPC was considered to be 5 mg for the healthy volunteers. 3. 3. Endocrinological research The serum prolactin level decreased dose-dependently in the OPC group, whereas it rose in the CPZ group. A significant negative correlation was recognized between the OPC-plasma level and serum prolactin level as well. 4. 4. Psychological tests In the Kraepelin test, a decrease in the average work quantity was observed in both groups, but it was less in the OPC group. 5. 5. Pharmacokinetic study From the pharmacokinetic parameters measured, two features were recognized: one was the slowness of Tmax (4–6 hours) and the other was the length of its biological half-life (56–88 hours). It was estimated that the plasma level of OPC-4392 would take 2 weeks to reach a steady state.