Characterization of 5-hydroxytryptamine1A properties of flesinoxan: In Vivo electrophysiology and hypothermia study
Characterization of 5-hydroxytryptamine1A properties of flesinoxan: In Vivo electrophysiology and hypothermia study
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氟辛克生 5-羟色胺1A 特性的表征：体内电生理学和低温研究
DOI：
10.1016/0028-3908(95)00098-q
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发表时间：
1995
影响因子：
4.7
通讯作者：
C. Montigny
中科院分区：
文献类型：
--
作者：
V. Hadrava;P. Blier;T. Dennis;C. Ortemann;C. Montigny
Flesinoxan是一种高亲和力和选择性5-羟色胺1A（5-HT 1A）配体，与阿扎匹隆类5-HT 1A激动剂不同，它不会产生α2-肾上腺素受体拮抗剂1-（2-嘧啶基）哌嗪。鉴于flesinoxan潜在的抗抑郁作用，本研究采用体内电生理学和低温范式来表征其在大鼠脑中的5-HT 1A特性。微电泳应用flesinoxan对CA 3锥体神经元放电活动的抑制作用被5-HT 1A拮抗剂BMY 7378的同时应用所阻断。与吉哌隆相比，flesinoxan抑制CA 3锥体神经元放电活动的功效显著更大。同时应用flesinoxan可拮抗5-HT对CA 3区锥体神经元的抑制作用，但对中缝背核5-HT神经元的抑制作用不明显，表明flesinoxan对突触后5-HT 1A受体起部分激动剂作用，对突触前5-HT 1A受体起完全激动剂作用。flesinoxan拮抗5-HT对CA_3区锥体神经元的作用与8-羟基-2-（二正丙基氨基）-四氢萘（8-OH-DPAT）相似，但明显强于吉哌隆。静脉注射flesinoxan可抑制CA 3区锥体神经元和中缝背核5-HT神经元的放电活动。然而，当与8-OH-DPAT相比时，需要显著更高剂量的flesinoxan。因此，测定了[3 H]flesinoxan和[3 H]8-OH-DPAT的急性脑渗透。静脉给药后9分钟，[3 H]8-OH-DPAT达到的脑浓度显著高于[3 H]flesinoxan。皮下注射flesinoxan和8-OH-DPAT产生剂量依赖性体温降低。预先给予非选择性5-HT_（1A）拮抗剂吲哚洛尔和5-HT_（12）拮抗剂麦角新碱可明显减轻菲辛克生引起的体温降低。用3 mg/kg的flesinoxan和0.5 mg/kg的8-OH-DPAT实现了类似程度的低温。flesinoxan的最大效应出现在30分钟后比8-OH-DPAT和褪色更慢。flesinoxan的5-HT 1A特性表明它可能是一种有效的抗焦虑/抗抑郁药物。
Flesinoxan is a high affinity and selective 5-hydroxytryptamine1A(5-HT1A) ligand which, unlike the 5-HT1Aagonists of the azapirone class, does not generate l-(2-pyrimidinyl)piperazine, an α2-adrenoreceptor antagonist. In view of potential antidepressant effects of flesinoxan, this study was undertaken to characterize its 5-HT1Aproperties in the rat brain using in vivo electrophysiology and hypothermia paradigms. The suppressant effect of microiontophoretic applications of flesinoxan on the firing activity of CA3pyramidal neurons was blocked by concomitant application of the 5-HT1Aantagonist BMY 7378. Compared to gepirone, the efficacy of flesinoxan to suppress the firing activity of CA3pyramidal neurons was significantly greater. While the coapplication of flesinoxan antagonized the suppressant effect of 5-HT on CA3pyramidal neurons, it failed to do so on dorsal raphe 5-HT neurons, indicating that flesinoxan acts as a partial agonist at postsynaptic and as a full agonist at presynaptic 5-HT1Areceptors. The capacity of flesinoxan to antagonize the effect of 5-HT on CA3pyramidal neurons was similar to that of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and significantly greater than that of gepirone. The intravenous administration of flesinoxan suppressed the firing activity of both CA3pyramidal neurons and dorsal raphe 5-HT neurons. However, when compared to 8-OH-DPAT, significantly higher doses of flesinoxan were required. The acute brain penetration of [3H]flesinoxan arid [3H]8-OH-DPAT was, therefore, determined. Nine minutes after intravenous administration, [3H]8-OH-DPAT reached significantly greater brain concentration than [3H]flesinoxan. Subcutaneous administration of flesinoxan and 8-OH-DPAT produced a dose-dependent hypothermia. The flesinoxaninduced hypothermia was significantly attenuated by prior administration of the non-selective 5-HT1Aantagonist pindolol and the 5-HT1 2antagonist methysergide. Similar degrees of hypothermia were achieved with 3 mg/kg of flesinoxan and 0.5 mg/kg of 8-OH-DPAT. The maximal effect of flesinoxan occurred 30 min later than that of 8-OH-DPAT and faded more slowly. The 5-HT1Aproperties of flesinoxan suggest that it may be an effective anxiolytic/antidepressant agent.
5-羟色胺1A介导的血清素合成抑制的受体储备：可能与5-羟色胺1A激动剂的抗焦虑特性有关。
影响因子：
3.6
作者：
Meller,E;Goldstein,M;Bohmaker,K
通讯作者：
Bohmaker,K
DOI：
10.1016/s0021-9258(19)39437-2
发表时间：
1990-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Paul R. Albert;Qun-Yong Zhou;H. V. Tol;J. Bunzow;O. Civelli
通讯作者：
Paul R. Albert;Qun-Yong Zhou;H. V. Tol;J. Bunzow;O. Civelli
5-Hydroxytryptamine 通过增加钾电导使 CA3 海马锥体细胞超极化。
影响因子：
2.5
作者：
Beck,SG;Choi,KC
通讯作者：
Choi,KC