Kinetics, Brain Uptake, and Receptor Binding of Tandospirone and Its Metabolite l-(2‐Pyrimidinyl)-piperazine

  title={Kinetics, Brain Uptake, and Receptor Binding of Tandospirone and Its Metabolite l-(2‐Pyrimidinyl)-piperazine},
  author={Lawrence G. Miller and Michael L. Thompson and J. Byrnes and David J. Greenhlatt and Anne Shemer},
  journal={Journal of Clinical Psychopharmacology},
Tandospirone is an azaspirodecanedione derivative under investigation as an antidepressant. Metabolism of tandospirone in humans and rodents leads to l-(2-pyrimidinyl)-piperazine (1-PP), presumed to have pharmacologic activity. To determine the relative contributions of tandospirone and 1-PP after tandospirone administration, we evaluated open-field activity, pharmacokinetics, and receptor binding of tandospirone and 1-PP in a mouse model. Tandospirone significantly reduced open-field activity… 

Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo

The results are the first evidence that systemic 5-HT1A receptor agonist administration produces a rapid increase in p-ERK levels in vivo, providing further insight into the signaling mechanisms of the 5- HT1A receptors.

Effect of tandospirone, a serotonin-1A receptor partial agonist, on information processing and locomotion in dizocilpine-treated rats

Findings suggest that behavioural changes induced by tandospirone are not fully blocked by 5-HT1A antagonists and that tandosphereirone (5 mg/kg) potentiates the effect of MK-801, and point to an interaction between NMDA and 5- HT1A receptors.

Simultaneous determination of tandospirone and its active metabolite, 1-[2-pyrimidyl]-piperazine in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

This method provided a fast, sensitive and selective analytical tool for quantification of tandospirone and its metabolite 1-PP in plasma necessary for the pharmacokinetic investigation.

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

Tandospirone suppresses impulsive action by possible blockade of the 5-HT1A receptor.

Tandospirone could be a therapeutic candidate for impulsivity-related disorders and may be due to the antagonistic action of the 5-HT1A receptor.

Role of tandospirone, a 5-HT1A receptor partial agonist, in the treatment of central nervous system disorders and the underlying mechanisms

The beneficial effect of tandospirone has been revealed on improvement of motor dysfunction of Parkinson's disease and cognitive deficits of schizophrenia either in monotherapy or in combination with other drugs.