The pharmacokinetics and pharmacodynamics of tandospirone in rats exposed to conditioned fear stress.

The 5-HT1, agonist tandospirone is generally thought to have a weak anxiolytic effect with a slow onset of action. Our recent clinical study suggested that a comparatively high dose of tandospirone has excellent anxiolytic efficacy and is without significant adverse effects. The present study was designed to clarify the relationship between the anxiolytic effect of tandospirone and its plasma and brain concentrations. The anxiolytic effect was estimated by determining the conditioned fear stress-induced freezing behavior in rats after tandospirone administration. Obvious correlations between anxiolytic effect and brain concentration of tandospirone were observed 0.5 and 4 h after tandospirone administration, while the anxiolytic effect was dependent on the plasma concentration of at 0.5 h but not 4 h after tandospirone administration. The plasma concentration was significantly correlated with the brain concentration. These findings suggest that the potency of the anxiolytic effect is dependent on both the plasma and brain concentration.