Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia.
Alpha7 Nicotinic Receptors as Therapeutic Targets in Schizophrenia.
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DOI：
10.1093/ntr/nty034
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发表时间：
2018-08
期刊：
影响因子：
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通讯作者：
J. Tregellas;Korey P. Wylie
中科院分区：
文献类型：
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作者：
J. Tregellas;Korey P. Wylie
虽然目前精神分裂症的治疗方法通常能大大缓解阳性症状，如幻觉，但其他症状，特别是认知缺陷，仍然存在，并导致患者遭受巨大痛苦和生活质量下降。在寻找治疗精神分裂症认知缺陷的新治疗方法时，最近的工作正在探索尼古丁受体神经生物学。在大量证据的支持下，在吸烟行为、遗传学、受体分布和功能、动物模型和烟碱对疾病症状的影响的研究的贡献下，α 7烟碱受体已成为潜在的治疗靶点。尽管在早期临床试验中有希望，但是，没有靶向尼古丁系统的药物在更大的3期试验中获得成功。简要回顾烟碱受体生物学和证据，导致追求α 7烟碱激动剂作为一种治疗策略，这篇综述将提供最新的临床试验的状态，讨论潜在的问题，可能会导致负面结果，并指出新的方向和有前途的进展，在开发α 7烟碱受体为基础的治疗精神分裂症的认知症状。通过研究α 7烟碱受体生物学和最近的努力，在临床试验中靶向受体，希望研究人员将有动力探索新的，有前途的方向集中在受体作为一种策略来治疗精神分裂症的认知症状。
While current treatments for schizophrenia often provide much relief for positive symptoms such as hallucinations, other symptoms, particularly cognitive deficits, persist and contribute to substantial suffering and reduced quality of life for patients. In searching for novel therapeutic avenues to treat cognitive deficits in schizophrenia, recent work is exploring nicotinic receptor neurobiology. Supported by a large body of evidence, with contributions from studies of smoking behaviors, genetics, receptor distribution and function, animal models and nicotinic effects on illness symptoms, the alpha7 nicotinic receptor has emerged as a potential therapeutic target. Despite promise in early clinical trials, however, no drug targeting nicotinic systems has succeeded in larger phase 3 trials. Following a brief review of nicotinic receptor biology and the evidence that has led to pursuit of alpha7 nicotinic agonism as a therapeutic strategy, this review will provide an update on the status of recent trials, discuss potential issues that may have contributed to negative outcomes, and point to new directions and promising advances in developing alpha7 nicotinic receptor-based treatment for cognitive symptoms in schizophrenia. IMPLICATIONS By examining alpha7 nicotinic receptor biology and recent efforts to target the receptor in clinical trials, it is hoped that investigators will be motivated to explore novel, promising directions focusing on the receptor as a strategy to treat cognitive symptoms in schizophrenia.