Comparative behavioural profiles of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in the murine elevated plus-maze
Comparative behavioural profiles of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) in the murine elevated plus-maze
复制标题
丁螺环酮及其代谢物 1-(2-嘧啶基)-哌嗪 (1-PP) 在小鼠高架十字迷宫中的比较行为特征
DOI：
10.1016/s0028-3908(97)00094-4
复制
发表时间：
1997
影响因子：
4.7
通讯作者：
R. Rodgers
中科院分区：
文献类型：
--
作者：
B. Cao;R. Rodgers
有人提出，体内代谢物 1-(2-嘧啶基)-哌嗪 (1-PP) 的形成可能是丁螺环酮用作抗焦虑剂的主要缺点。为了检验这一假设，在小鼠焦虑高架十字迷宫测试中，将丁螺环酮单独或与普罗迪芬（一种肝微粒体酶抑制剂）预处理的效果与 1-PP 的效果进行了对比。在 3.0 mg/kg（但不是更低剂量）时，丁螺环酮本身具有适度的抗焦虑样作用（增加张开手臂的百分比；减少伸展姿势和平背姿势），与增加的梳理和不动有关。然而，在 Proadifen 预处理的小鼠中，丁螺环酮仅产生行为抑郁，在 1.0 和 3.0 mg/kg 剂量下均具有明显的效果。由于普罗阿芬阻断丁螺环酮向 1-PP 的生物转化，这些数据表明丁螺环酮在小鼠十字迷宫中的任何抗焦虑活性可能归因于其主要活性代谢物。与这一假设一致，1-PP（0.5-13.5 mg/kg）对常规和行为学测量均产生剂量依赖性抗焦虑作用，且不会因运动障碍而混淆。讨论了与生化和电生理学研究相关的结果，表明 1-PP 对 5-HT1A 受体具有直接作用。
It has been suggested that in vivo formation of the metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) may be a major drawback in the use of buspirone as an anti-anxiety agent. To test this hypothesis, the effects of buspirone, alone or with proadifen (an inhibitor of liver microsomal enzymes) pretreatment, were contrasted with those of 1-PP in the murine elevated plus-maze test of anxiety. At 3.0 mg/kg (but not lower doses), buspirone per se had modest anxiolytic-like effects (increased percentage of open arm entries; reduced stretched-attend postures and flatback approach) that were associated with increased grooming and immobility. However, in proadifen-pretreated mice, buspirone produced behavioural depression only, with marked effects evident both at 1.0 and 3.0 mg/kg. As proadifen blocks the biotransformation of buspirone to 1-PP, these data suggest that any anxiolytic activity of buspirone in the murine plus-maze may be attributable to its principal active metabolite. Consistent with this hypothesis, 1-PP (0.5–13.5 mg/kg) produced dosedependent anti-anxiety effects on both conventional and ethological measures that were not confounded by motoric impairment. Results are discussed in relation to biochemical and electrophysiological studies suggesting that 1-PP has a direct action at 5-HT1Areceptors.