Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats.

To investigate the effects of zopiclone on the central nervous system, we examined the effects of zopiclone on brain monoamines such as dopamine (DA), noradrenaline (NA) and serotonin (5-HT) and their metabolites such as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), as well as locomotor activity in comparison with those of nitrazepam and flurazepam. Zopiclone in a dose of 10 mg/kg (p.o.) significantly reduced it (p less than 0.01) in 30 min and the reduced locomotor activity persisted until 180 min. The reducing effect on locomotor activity by zopiclone was similar to that of nitrazepam and more potent than flurazepam. The effects of zopiclone on brain monoamines (MA) were examined. No significant changes in DA, NA and 5-HT were observed, but HVA and 5-HIAA were reduced. A fluorescent-histochemical study conducted simultaneously revealed almost the same results as the biochemical test results. From the facts that zopiclone inhibited locomotor activity in rats, and inhibited brain DA and 5-HT turnover, the mechanism of action of zopiclone in brain MA neurons seems to be similar to that of benzodiazepine derivatives.