Antidepressant-like activity of YL-0919: a novel combined selective serotonin reuptake inhibitor and 5-HT1A receptor agonist.
Antidepressant-like activity of YL-0919: a novel combined selective serotonin reuptake inhibitor and 5-HT1A receptor agonist.
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YL-0919 的抗抑郁样活性：一种新型选择性血清素再摄取抑制剂和 5-HT1A 受体激动剂的组合
DOI：
10.1371/journal.pone.0083271
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li YF
中科院分区：
文献类型：
--
作者：
Chen HX;Jin ZL;Zhang LM;Xue R;Xu XD;Zhao N;Qiu ZK;Wang XW;Zhang YZ;Yang RF;Li YF
有研究表明，选择性5-羟色胺再摄取抑制剂和5-HT1a受体激动剂的联合用药可能成为提高抗抑郁药疗效的新策略。本研究旨在研究YL-0919的药理作用，YL-0919是一种对5-羟色胺转运体和5-HT1A受体具有高亲和力和选择性的新型合成化合物。我们进行了体外结合和功能测试以及体内行为测试，以评估YL-0919的药理特性和抗抑郁药样疗效。YL-0919在体外对大鼠皮质5-HT1a受体和5-羟色胺转运体均有较高的亲和力。对Forsklin刺激的cAMP生成有抑制作用，对大鼠皮质突触体和重组细胞的5-羟色胺摄取均有抑制作用。在急性PO之后。给药后极低剂量的YL-0919可缩短小鼠悬尾实验和强迫游泳实验中的不动时间，但对小鼠旷场活动无明显影响。此外，选择性5-HT1a受体拮抗剂Way-100635(0.3 mg/kg)可显著阻断YL-0919的悬尾实验和强迫游泳实验。此外，慢性YL-0919治疗可显著逆转慢性应激大鼠的抑郁样行为。这些结果表明，YL-0919作为5-HT1a受体激动剂和5-羟色胺摄取阻滞剂，对5-羟色胺能系统具有双重作用，在动物模型中表现出显著的抗抑郁作用。因此，YL-0919可作为治疗抑郁症的新选择。
It has been suggested that drugs combining activities of selective serotonin reuptake inhibitor and 5-HT1A receptor agonist may form a novel strategy for higher therapeutic efficacy of antidepressant. The present study aimed to examine the pharmacology of YL-0919, a novel synthetic compound with combined high affinity and selectivity for serotonin transporter and 5-HT1A receptors. We performed in vitro binding and function assays and in vivo behavioral tests to assess the pharmacological properties and antidepressant-like efficacy of YL-0919. YL-0919 displayed high affinity in vitro to both 5-HT1A receptor and 5-HT transporter prepared from rat cortical tissue. It exerted an inhibitory effect on forskolin-stimulated cAMP formation and potently inhibited 5-HT uptake in both rat cortical synaptosomes and recombinant cells. After acute p.o. administration, very low doses of YL-0919 reduced the immobility time in tail suspension test and forced swimming test in mice and rats, with no significant effect on locomotor activity in open field test. Furthermore, WAY-100635 (a selective 5-HT1A receptor antagonist, 0.3 mg/kg) significantly blocked the effect of YL-0919 in tail suspension test and forced swimming test. In addition, chronic YL-0919 treatment significantly reversed the depressive-like behaviors in chronically stressed rats. These findings suggest that YL-0919, a novel structure compound, exerts dual effect on the serotonergic system, as both 5-HT1A receptor agonist and 5-HT uptake blocker, showing remarkable antidepressant effects in animal models. Therefore, YL-0919 may be used as a new option for the treatment of major depressive disorder.
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影响因子：
5
作者：
Dutta, Aloke K.;Ghosh, Balaram;Reith, Maarten E. A.
通讯作者：
Reith, Maarten E. A.
影响因子：
2.7
作者：
Bekris, S;Antoniou, K;Papadopoulou-Daifoti, Z
通讯作者：
Papadopoulou-Daifoti, Z
DOI：
10.3109/10401239509149042
发表时间：
1995-09-01
期刊：
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists
影响因子：
--
作者：
Harvey, K V;Balon, R
通讯作者：
Balon, R
影响因子：
3.6
作者：
An, Lei;Zhang, You-Zhi;Li, Yun-Feng
通讯作者：
Li, Yun-Feng
影响因子：
7.6
作者：
Bondi, Corina O.;Rodriguez, Gustavo;Morilak, David A.
通讯作者：
Morilak, David A.