The pharmacokinetics and pharmacodynamics of tandospirone in rats exposed to conditioned fear stress
The pharmacokinetics and pharmacodynamics of tandospirone in rats exposed to conditioned fear stress
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DOI：
10.1016/j.euroneuro.2005.11.009
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发表时间：
2006-07-01
影响因子：
5.6
通讯作者：
Higuchi, Shun
中科院分区：
文献类型：
--
作者：
Nishitsuji, Kyoko;to, Hide To;Higuchi, Shun
5-HT1激动剂坦度螺酮通常被认为具有微弱的抗焦虑作用，作用开始缓慢。我们最近的临床研究表明，较大剂量的坦度螺酮具有良好的抗焦虑效果，且没有明显的不良反应。本研究旨在阐明坦度螺酮的抗焦虑作用与其血浆和脑内浓度之间的关系。通过测定给予坦度螺酮后大鼠条件性恐惧应激诱导的冰冻行为来评价其抗焦虑作用。坦度螺酮的抗焦虑作用与给药后0.5h和4h的脑内药物浓度有明显的相关性，但在给药后0.5h的抗焦虑作用不依赖于给药后4h的血药浓度。血药浓度与脑血药浓度呈显著正相关。这些发现表明，抗焦虑作用的效力取决于血浆和脑中的浓度。(C)2005年爱思唯尔和ECNP。版权所有。
The 5-HT1, agonist tandospirone is generally thought to have a weak anxiolytic effect with a stow 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. (c) 2005 Elsevier B.V. and ECNP. All rights reserved.