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α7 型烟碱型乙酰胆碱受体在精神分裂症患者认知加工过程中的作用。

The role of the α7 nicotinic receptor in cognitive processing of persons with schizophrenia.

机构信息

VA Boston Healthcare System, Brockton Division, Brockton, Massachusetts 02301, USA.

出版信息

Curr Opin Psychiatry. 2012 Mar;25(2):103-8. doi: 10.1097/YCO.0b013e3283503637.

Abstract

PURPOSE OF REVIEW

Cognitive abilities are established as major deficits in those with schizophrenia and represent significant impediments toward successful psychosocial functioning within the community. Pharmacological treatments have historically focused on reducing the positive and negative symptoms of schizophrenia, with recent increased attention to developing agents to improve cognition as a treatment outcome. This review will highlight the recent advances in developing agents that act at neuronal α7 nicotinic acetylcholine receptors (nAChRs).

RECENT FINDINGS

A number of agents have demonstrated improvements in cognitive deficits in studies using both preclinical and clinical models. Evidence suggests that α7 nAChR activation impacts rule acquisition and initial learning in preclinical models. Preclinical studies indicate improved spatial working memory and reversal of phencyclidine-induced learning and memory deficits. Clinical studies indicate normalization of neuronal default network activity using functional magnetic resonance imaging methods. In addition, research on new agents developed to improve cognition suggests improved cognitive functioning in multiple domains (e.g., attention, memory, executive functioning, sensory gating and overall cognition) and promising safety profiles of additional agents.

SUMMARY

Improvements in cognitive functioning within preclinical and clinical studies of schizophrenia are evident through the use of α7 nAChR agonists, while positive allosteric modulators may gain increased attention in the future.

摘要

目的综述

认知能力在精神分裂症患者中已被确定为主要缺陷,这对他们在社区中成功进行社会心理功能有重大影响。在历史上,药物治疗一直侧重于减少精神分裂症的阳性和阴性症状,最近越来越关注开发改善认知作为治疗结果的药物。这篇综述将重点介绍开发作用于神经元α7 烟碱型乙酰胆碱受体(nAChR)的药物的最新进展。

最近的发现

许多药物在使用临床前和临床模型的研究中都证明了认知缺陷的改善。有证据表明,α7 nAChR 激活会影响临床前模型中的规则获取和初始学习。临床前研究表明,空间工作记忆得到改善,逆转了苯环己哌啶引起的学习和记忆缺陷。临床研究表明,使用功能磁共振成像方法可以使神经元默认网络活动正常化。此外,为改善认知功能而开发的新药物的研究表明,多种认知领域(例如注意力、记忆、执行功能、感觉门控和整体认知)的认知功能得到改善,并且其他药物具有有前景的安全性特征。

总结

通过使用α7 nAChR 激动剂,在精神分裂症的临床前和临床研究中明显改善了认知功能,而正变构调节剂在未来可能会受到更多关注。

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