Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors
Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors
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DOI：
10.1016/j.ejphar.2005.01.032
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发表时间：
2005-03-21
影响因子：
5
通讯作者：
Fuentes, JA
中科院分区：
文献类型：
--
作者：
Delgado, M;Caicoya, AG;Fuentes, JA
S-（-）-2-[[4-（napht-1-yl）piperazin-1-yl]methyl]-1，4-dioxoperhydropyrrofolo [1，2-alpha]-pyrazine（CSP-2503）是一种5-HT受体配体，对5-HT 1A、5-HT 2A和5-HT 3受体具有选择性和高亲和力。CSP-2503降低小鼠直肠温度和5-HT神经元下丘脑活动，降低大鼠中缝核细胞的电活动，并阻断转染人5-HT 1A受体的HeLa细胞中由forskolin诱导的腺苷酸环化酶活性的增强。该化合物还阻断由5-HT 2A/2c受体激动剂2，5-二甲氧基-4-碘苯丙胺（DOI）诱导的头部抽搐。CSP-2503可阻止5-HT 3受体激动剂2-甲基-5-HT引起的豚鼠回肠收缩。对2-甲基-5-羟色胺诱发的麻醉大鼠心动过缓反射也有明显的抑制作用。在明/暗盒和社会互动测试中，CSP-2503呈现抗焦虑活性，这是5-HT激动剂和5-HT 3拮抗剂共有的作用。综上所述，这些结果表明CSP-2503是一种新的5-HT受体激动剂，具有5-HT 2A和5-HT 3受体拮抗剂活性，可用于许多与焦虑相关的病症。(c)2005 Elsevier B. V.保留所有权利。
S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-alpha]-pyrazine (CSP-2503) is a serotonin (5-HT) receptor ligand with selectivity and high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors. CSP-2503 reduced rectal temperature and 5-HT neuronal hypothalamic activity in mice, decreased electrical activity of raphe nuclei cells in rats and blocked the enhancement of adenylate cyclase activity induced by forskolin in HeLa cells transfected with the human 5-HT1A receptor. This compound also blocked head-twitches induced by the 5-HT2A/2c receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). Contractions of guinea pig ileum induced by the 5-HT3 receptor agonist 2-methyl-5-HT were prevented by CSP-2503. Moreover, it reduced the bradycardia reflex induced by 2-methyl-5-HT in anaesthetized rats. In the light/dark box and social interaction tests, CSP-2503 presented anxiolytic activity, an action shared by 5-HT, agonists and 5-HT3 antagonists. Taken together, these results suggest that CSP-2503 is a new 5-HT, receptor agonist with 5-HT2A and 5-HT3 receptor antagonist activities that might be useful in a number of conditions associated with anxiety. (c) 2005 Elsevier B.V. All rights reserved.