Anxiolytic-like activity of R(+)- and S(-)-zacopride in mice.

The effects of the optical isomers of zacopride were assessed in mice in a fully automated two-compartment light/dark apparatus. A significant increase in time spent in the lit area was used as an indication of anxiolytic-like action. Intraperitoneal (i.p.) doses of R(+)-zacopride from 0.00001 to 10.0 mg/kg and S(-)-zacopride from 0.01 to 1.0 mg/kg produced significant anxiolytic-like activity. Oral (p.o.) doses of the R(+) isomer from 0.00001 to 10.0 mg/kg and S(-)isomer from 0.1 to 1.0 mg/kg also generated antianxiety-like action. In addition, R(+)-zacopride (0.0001 mg/kg) was evaluated for time course effects after i.p. and p.o. administration. By either route of injection, the onset to action of R(+)-zacopride was 0.5 h, while the duration of effect was greater than or equal to 16 h. It was concluded that R(+)-zacopride is a potent and long-acting drug and that it is principally responsible for the anxiolytic-like activity of racemic zacopride.