title: In vivo drug action of tandospirone at 5-HT1A receptor examined using positron emission tomography and neuroendocrine response.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The aim of this study was to assess the effect of tandospirone on in vivo 5-HT(1A) receptor binding of [(11)C]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 [(11)C]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 [(11)C]WAY 100635 binding following the administration of 30 mg or 60 mg tandospirone.
  
  
  CONCLUSIONS
  Despite the significant effect on growth hormone and body temperature, a clinical dose of tandospirone had a negligible effect on [(11)C]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.
authors.affiliation: Crest, Japan Science and Technology Corporation, Kawaguchi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakayama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Okubo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichimiya
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasuno
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Saijo
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D054833:Isoindoles; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry; D011743:Pyrimidines / Q000494:pharmacology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000737:chemistry; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors; D014055:Tomography, Emission-Computed / Q000379:methods*
chemical_list: D054833:Isoindoles; D010879:Piperazines; D011725:Pyridines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C055267:tandospirone; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D013006:Growth Hormone; D006854:Hydrocortisone