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

Kyoko Nishitsuji, Hideto To, Tokiko Shimizu, Yuko Yanase, Tomomi Yamada, Chiaki Hara, Kazunori Mine*, Shun Higuchi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)376-382
Number of pages7
JournalEuropean Neuropsychopharmacology
Volume16
Issue number5
DOIs
StatePublished - 2006/07

Keywords

  • Brain concentration
  • Freezing behavior
  • Plasma level
  • Rat
  • Tandospirone

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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