In vivo drug action of tandospirone at 5-HT_1A receptor examined using positron emission tomography and neuroendocrine response

Abstract

Rationale. Tandospirone is a selective 5-hydroxytryptamine (HT)_1A receptor agonist and is clinically used as an anxiolytic in Japan. However, there are no data concerning the occupancy of these receptors by tandospirone in the living human brain.

Objectives. The aim of this study was to assess the effect of tandospirone on in vivo 5-HT_1A receptor binding of [¹¹C]WAY 100635 using positron emission tomography (PET) and the neuroendocrine effect.

Methods. In the PET study, seven healthy volunteers were scanned three times following an oral dose of placebo or tandospirone (30 mg or 60 mg). The binding potential of [¹¹C]WAY 100635 was estimated for six regions: prefrontal cortex, temporal cortex, anterior cingulate cortex, parietal cortex, hippocampus and dorsal raphe nucleus. In the neuroendocrine study, six volunteers received a single oral dose of tandospirone (60 mg) or placebo in a randomized double-blind, cross-over design, and then the plasma levels of growth hormone and cortisol and the body temperature were measured.

Results. Tandospirone (60 mg) induced a significant decrease in body temperature and an increase in the plasma concentration of growth hormone. However, there was no significant reduction of [¹¹C]WAY 100635 binding following the administration of 30 mg or 60 mg tandospirone.

Conclusion. Despite the significant effect on growth hormone and body temperature, a clinical dose of tandospirone had a negligible effect on [¹¹C]WAY 100635 binding. This indicates that the agonist produces a pharmacological effect without measurable occupancy, and a new index other than occupancy will be required for the in vivo evaluation of agonists.