Review Article

非多巴胺能药物治疗精神分裂症的发现和开发:临床前和早期临床研究概述。

卷 26, 期 25, 2019

页: [4885 - 4913] 页: 29

弟呕挨: 10.2174/0929867326666190710172002

价格: $65

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摘要

精神分裂症是一种慢性精神病,影响全世界约100人中的1人,并导致持续的情绪和认知障碍。 未经治疗的精神分裂症会导致生活质量下降和过早死亡。 尽管多巴胺D2受体拮抗剂对精神分裂症阳性症状的临床疗效支持该疾病的多巴胺假说,但阴性和认知症状对这些药物的耐药性在其病理生理学方面牵涉其他系统。 许多研究表明,谷氨酸稳态的异常可能导致所有三组精神分裂症症状。 科学考虑还包括对γ-氨基丁酸能和血清素能神经传递的紊乱以及免疫系统的作用。 这篇综述的目的是更新有关非多巴胺能药物发现和开发的最新报告,这些药物可以减轻精神分裂症的阳性,阴性和认知症状,并且可以替代目前使用的抗精神病药。 这篇综述收集了针对代谢型谷氨酸受体,γ-氨基丁酸A型受体,α7烟碱型乙酰胆碱受体,1型甘氨酸转运蛋白和糖原合酶激酶3的代表性化合物的化学结构,以及体外和体内研究结果表明 精神分裂症的疗效。 还提出了评估试验化合物安全性和有效性的临床试验结果。 最后,已经关注具有5-羟色胺受体亲和力或磷酸二酯酶抑制活性的多功能配体,作为寻找精神分裂症患者专用药物的新策略

关键词: 精神分裂症,mGlu受体配体,GABAA受体配体,α7nACh受体激动剂,GlyT1抑制剂,GSK-3抑制剂,PDE抑制剂,5-HT受体配体。

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