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用α7烟碱型激动剂治疗精神分裂症症状:从小鼠到人类

Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men.

作者信息

Olincy Ann, Stevens Karen E

机构信息

Department of Psychiatry, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA.

出版信息

Biochem Pharmacol. 2007 Oct 15;74(8):1192-201. doi: 10.1016/j.bcp.2007.07.015. Epub 2007 Jul 17.

Abstract

Current antipsychotic treatments fail to fully address the range of symptoms of schizophrenia, particularly with respect to social and occupational dysfunctions. Recent work has highlighted the role of nicotinie in both cognitive and attentional deficits as well as deficient processing of repetitive sensory information. The predilection for schizophrenia patients to be extremely heavy cigarette smokers may be related to their attempt to compensate for a reduction in hippocampal alpha7 nicotinic cholinergic receptors by delivering exogenous ligand to the remaining receptors. Studies in rodent models of both learning and memory deficits and deficits in sensory inhibition have confirmed a role for the alpha7 subtype of the nicotinic cholinergic receptor in these processes. Rodent studies also demonstrated the efficacy of a selective partial alpha7 nicotinic agonist, DMXBA, to improve these deficits. Subsequent human clinical trials demonstrated improved sensory inhibition in 12 schizophrenia patients and showed improvement in several subtests of the RBANS learning and memory assessment instrument. These data suggest that therapeutic agents selected for alpha7 nicotinic activity may have utility in treating certain symptoms of schizophrenia.

摘要

目前的抗精神病药物治疗未能充分解决精神分裂症的一系列症状,尤其是在社交和职业功能障碍方面。最近的研究突出了烟碱在认知和注意力缺陷以及重复性感觉信息处理不足方面的作用。精神分裂症患者极易成为重度吸烟者,这可能与他们试图通过向剩余受体提供外源性配体来补偿海马体α7烟碱型胆碱能受体减少有关。对学习和记忆缺陷以及感觉抑制缺陷的啮齿动物模型的研究证实了烟碱型胆碱能受体α7亚型在这些过程中的作用。啮齿动物研究还证明了选择性部分α7烟碱激动剂DMXBA改善这些缺陷的功效。随后的人体临床试验表明,12名精神分裂症患者的感觉抑制得到改善,并且在RBANS学习和记忆评估工具的几个子测试中也有改善。这些数据表明,针对α7烟碱活性选择的治疗药物可能对治疗精神分裂症的某些症状有用。

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