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COMPOUNDS MODULATING ASTROCYTIC RELEASE OF SUBSTANCES THROUGH CONNEXINS AND PANNEXINS AND TREATMENT OF PSYCHIATRIC DISORDERS

机译:通过连接蛋白和粘连蛋白调节物质的星形胶质细胞释放并治疗精神分裂症的化合物

摘要

The present invention is related to the use of compounds or pharmaceutically acceptable salts thereof that modulate astrocytic release of substances through connexin and pannexin hemichannels, for the treatment of psychiatric disorders. Compounds or pharmaceutically acceptable salts thereof used in the present invention comprise any compound that differentially modulates, blocks, opens, inhibits, and/or activates connexin and/or pannexin hemichannels from astrocytes while not affecting gap junctions. The invention is also related to a method for treating psychiatric disorders, comprising administering to a mammal or human a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof, that modulates astrocytic release of substances through connexin and pannexin hemichannels. Pharmaceutical compositions and a screening method are also considered in the present invention. Examples are shown for connexin 43, connexin 30 and pannexin 1 hemichannel modulators shown not to affect gap junctions, in the form of both non peptide compounds and peptides which were tested in different models for psychiatric disorders, comprising PTSD, memory, anxiety and depression.
机译:本发明涉及通过连接蛋白和泛新半通道调节化合物的星形细胞释放的化合物或其药学上可接受的盐在治疗精神疾病中的用途。用于本发明的化合物或其药学上可接受的盐包括差异调节,阻断,打开,抑制和/或激活来自星形胶质细胞的连接蛋白和/或泛神经毒素半通道而不会影响间隙连接的任何化合物。本发明还涉及一种治疗精神疾病的方法,该方法包括向哺乳动物或人施用治疗有效量的化合物或其药学上可接受的盐,其调节通过连接蛋白和泛神经毒素半通道的物质的星形细胞释放。在本发明中还考虑了药物组合物和筛选方法。显示了连接蛋白43,连接蛋白30和泛肽1半通道调节剂的实例,其以非肽化合物和肽的形式显示为不影响间隙连接,所述肽在包括PTSD,记忆,焦虑和抑郁的不同精神疾病模型中进行了测试。

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