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评估用于支持首次在人身上进行临床试验的临床前抗精神病药物模型
Thi Viet Ha Nguyen1,2,3, Declan P McKernan1,3, John P Kelly1,3
1Discipline of Pharmacology and Therapeutics, School of Pharmacy & Medical Sciences, University of Galway, Galway, Ireland.
British journal of pharmacology
|December 23, 2025
概括
由于转化挑战,对精神分裂症的动物模型在预测抗精神病药物的有效性方面取得了有限的成功. 完善这些模型并纳入生物标志物对于开发有效治疗方法至关重要.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 精神分裂症是一种复杂的精神疾病,目前的治疗方法不足.
- 抗精神病药物开发面临挑战,原因是临床前模型和临床试验之间的翻译差距.
研究的目的:
- 在过去30年中,系统地审查使用动物模型和行为分析来评估抗精神病药物的有效性.
- 分析这些模型在捕捉精神分裂症的复杂性方面的翻译挑战和局限性.
主要方法:
- 对制药行业使用动物模型进行抗精神病药物疗效测试的审查.
- 通过临床前数据分析监管提交和临床发展.
- 检查纳入标准对抗精神病药物疗效测试的影响.
主要成果:
- 许多在动物模型中有效的新型化合物在人类临床试验中失败.
- 模型选择和行为终点的局限性导致了转化差距.
- 动物模型难以捕捉人类精神分裂症的全部异质性.
结论:
- 目前的动物模型对抗精神病药物成功的预测价值有限.
- 完善模型选择,行为终点和整合生物标志物至关重要.
- 需要改进临床前策略,以提高新型抗精神病药物的成功率.
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