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Review Article

发现中枢神经系统相关疾病的PDE10A抑制剂的进展。 第2部分：专注于精神分裂症

卷 20, 期 16, 2019

页: [1652 - 1669] 页: 18

弟呕挨: 10.2174/1389450120666190801114210

价格: $65

摘要

精神分裂症是一种使人衰弱的精神障碍，患病率相对较高（约1％），在此期间会出现积极的表现（例如精神病状态）和消极的症状（例如退出社交生活）。此外，一些研究人员认为认知障碍是精神分裂症症状的一个独特领域。多巴胺活性的不平衡，即纹状体中这种神经递质的过度释放和额叶前额皮质中的量不足，被认为是造成这些组表现的部分原因。第二代抗精神病药目前是精神分裂症的标准治疗方法。然而，现有的治疗有时是无效的，并且具有严重的副作用，例如锥体外系症状。因此，迫切需要寻找该疾病的替代治疗选择。这篇综述总结了最近在磷酸二酯酶10A（PDE10A）的临床前和临床研究的结果，磷酸二酯酶10A在哺乳动物纹状体中高度表达，作为治疗精神分裂症的潜在药物靶标。根据文献数据，不仅选择性的PDE10A抑制剂而且双重的PDE2A / 10A和PDE4B / 10A抑制剂以及具有PDE10A抑制能力的多功能配体都是可以结合抗精神病药，预知性药物和抗抑郁药功能的化合物。因此，设计此类化合物可能构成精神分裂症潜在药物的新研究方向。尽管先前的选择性PDE10A抑制剂治疗精神分裂症的临床试验失败，但目前正在临床上研究具有这种作用机制的新化合物，因此，仍需要寻找选择性和多靶点PDE10A的新抑制剂。

关键词: PDE10A抑制剂，多功能配体，抗精神病活性，认知活性，精神分裂症，临床试验。

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