Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety
Lack of efficacy of melanin-concentrating hormone-1 receptor antagonists in models of depression and anxiety
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DOI：
10.1016/j.ejphar.2006.04.043
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发表时间：
2006-07-01
影响因子：
5
通讯作者：
Rueter, Lynne E.
中科院分区：
文献类型：
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作者：
Basso, Ana M.;Bratcher, Natalie A.;Rueter, Lynne E.
这项研究的目的是验证黑色素浓缩激素(MCH)-I受体拮抗剂作为一种潜在的情绪障碍治疗方法。我们试图复制先前报道的SNAP-7941的作用，并将研究扩大到其他三种口服生物可用的MCH-1受体拮抗剂，这些药物具有良好的脑渗透性。Snap-7941(3-30 mg/kg，ip)和T-226296(5-60 mg/kg，P.O.)(+/-外消旋体)，在大鼠强迫游泳和小鼠尾悬吊实验中进行评价。(+)SNAP-7941(3-10 mg/kg，P.O.)如先前报道的那样，还在修改的5分钟大鼠强迫游泳方案中进行了测试。A-665798(3-30 mg/kg，P.O.)和A-777903(3-30 mg/kg，P.O.)在小鼠尾部悬吊和大鼠伏格尔试验中进行了试验。在测试的范例中，没有一种化合物显示出有意义的疗效。四种结构不同的MCH-1受体拮抗剂缺乏疗效，不支持通过这种作用机制治疗抑郁症/焦虑症。(C)2006爱思唯尔B.V.保留所有权利。
The aim of this study was to validate melanin-concentrating hormone (MCH)- I receptor antagonism as a potential treatment of mood disorders. We attempted to replicate the effects previously reported with SNAP-7941 and expanded the investigation to three other orally bioavailable MCH-1 receptor antagonists with good brain penetration. SNAP-7941 (3-30 mg/kg, i.p.) and T-226296 (5-60 mg/kg, p.o.) (+/- racemate), were evaluated in the rat forced swim and mouse tail suspension tests. (+)SNAP-7941 (3-10 mg/kg, p.o.) was also tested in a modified 5-min rat forced swim protocol as previously reported. A-665798 (3-30 mg/kg, p.o.) and A-777903 (3-30 mg/kg, p.o.) were tested in mouse tail suspension and rat Vogel tests. None of the compounds showed meaningful efficacy in the paradigms tested. The lack of efficacy with four structurally different MCH-1 receptor antagonists does not support a role for therapeutic treatment of depression/anxiety via this mechanism of action. (c) 2006 Elsevier B.V All rights reserved.