Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia
Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophrenia
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DOI：
10.1176/appi.ajp.2008.06091591
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发表时间：
2008-08-01
影响因子：
17.7
通讯作者：
Felder, Christian C.
中科院分区：
文献类型：
--
作者：
Shekhar, Anantha;Potter, William Z.;Felder, Christian C.
目的：在精神分裂症的治疗方面，尤其是在认知障碍、阴性综合征和认知功能的治疗方面，存在显著的未满足的需求。临床前数据表明，对乙酰胆碱毒蕈碱受体具有选择性亲和力的激动剂提供了治疗精神分裂症的潜在新机制。作者研究了xanomeline，一个相对选择性的毒蕈碱型1和4型（M-1和M-4）受体激动剂，以确定这种药物是有效的精神分裂症的治疗方法：在这项试点研究中，作者研究了xanomeline的疗效与精神分裂症（N=20）的临床结果，利用双盲，安慰剂对照，4周的治疗设计。结果的措施包括阳性和阴性症状量表（PANSS）的精神分裂症，简明精神病评定量表（BPRS），临床总体印象（CGI）量表，和一个测试电池设计来衡量认知功能的精神分裂症patients with schizophrenia.Results：主题与咕诺美林治疗的总BPRS评分和总PANSS评分显着优于安慰剂组的主题。在认知测试电池中，受试者在依诺美林组中表现出最稳健的言语学习和短期记忆function.Conclusions的措施的改善：这些结果支持进一步调查的依诺美林作为一种新的方法来治疗精神分裂症。
Objective: There are significant unmet needs in the treatment of schizophrenia, especially for the treatment of cognitive impairment, negative syndrome, and cognitive function. Preclinical data suggest that agonists with selective affinity for acetylcholine muscarinic receptors provide a potentially new mechanism to treat schizophrenia. The authors studied xanomeline, a relatively selective muscarinic type 1 and type 4 (M-1 and M-4) receptor agonist, to determine if this agent is effective in the treatment of schizophrenia.Method: In this pilot study, the authors examined the efficacy of xanomeline on clinical outcomes in subjects with schizophrenia (N=20) utilizing a double-blind, placebo-controlled, 4-week treatment design. Outcome measures included the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression (CGI) scale, and a test battery designed to measure cognitive function in patients with schizophrenia.Results: Subjects treated with xanomeline did significantly better than subjects in the placebo group on total BPRS scores and total PANSS scores. In the cognitive test battery, subjects in the xanomeline group showed improvements most robustly in measures of verbal learning and short-term memory function.Conclusions: These results support further investigation of xanomeline as a novel approach to treating schizophrenia.