Nicotinic Receptors and Schizophrenia

烟碱受体和精神分裂症

• 批准号: 8195971
• 负责人: Robert Freedman
• 金额: --
• 依托单位: VA EASTERN COLORADO HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195971
• 关键词: Abstinence; Adverse effects; Agonist; Clinical Research; Consensus; Dopamine D2 Receptor; Drug Formulations; Funding; Investigation; National Institute of Mental Health; Neurocognition; Neurocognitive; Nicotinic Agonists; Nicotinic Receptors; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Schizophrenia; Testing; Veterans; Work; alpha-bungarotoxin receptor; anabaseine; base; cigarette smoking; cognitive rehabilitation; disability; drug candidate; improved; meetings; new therapeutic target; programs; public health relevance; treatment response

DESCRIPTION (provided by applicant): Project Summary Schizophrenia is a leading cause of disability for Veterans. The CATIE studies have demonstrated that the current treatment of schizophrenia does not produce results that are fully satisfactory to either clinicians or their patients, because both groups repeatedly switched medications to try to obtain better treatment response with fewer side effects. Cognitive rehabilitation efforts show similar ceiling effects. All currently available drugs have D2-dopamine receptor blockade as their primary pharmacological effect. The NIMH MATRICS program was established to find new therapeutic targets for schizophrenia, in addition to dopamine-D2 receptor blockade, because pharmaceutical companies have been slow to develop such targets. The NIMH emphasis was on candidate mechanisms that would improve neurocognition in schizophrenia. At the NIIMH-sponsored MATRICS consensus meeting, alpha7-nicotinic acetylcholine receptor agonism was selected as the leading candidate for new drug investigation, based on the findings of this Merit Review project. No pharmaceutical company has completed a clinical study of an alpha7-nicotinic agonist in schizophrenia. PUBLIC HEALTH RELEVANCE: Project Narrative Work by this Merit Review project in the current funding period has identified a proof of principle drug candidate, 3-2,4 dimethoxybenzylidene anabaseine (DMXB-A), that is a safe and apparently effective agonist for the alpha7-nicotinic acetylcholine receptor. The hypothesis to be tested in the proposed renewal is that DMXB-A will produce significant neurocognitive improvement in Veterans with schizophrenia.

描述（由申请人提供）： 项目摘要 精神分裂症是退伍军人残疾的主要原因。 CATIE研究表明，目前精神分裂症的治疗并没有产生令临床医生或其患者完全满意的结果，因为两组患者都反复更换药物，试图获得更好的治疗反应和更少的副作用。认知康复工作也显示出类似的天花板效应。目前所有药物均以D2-多巴胺受体阻断为主要药理作用。 NIMH MATRICS 计划的建立是为了除了多巴胺-D2 受体阻断之外寻找精神分裂症的新治疗靶点，因为制药公司在开发此类靶点方面进展缓慢。 NIMH 的重点是改善精神分裂症神经认知的候选机制。在 NIIMH 主办的 MATRICS 共识会议上，根据该优点评审项目的结果，α7-烟碱乙酰胆碱受体激动剂被选为新药研究的主要候选药物。尚无制药公司完成 α7-烟碱激动剂治疗精神分裂症的临床研究。 公共卫生相关性： 项目叙述 该优点审查项目在当前资助期间的工作已确定了一种主要候选药物的证明，3-2,4 二甲氧基亚苄基阿那巴辛 (DMXB-A)，它是一种安全且明显有效的 α7-烟碱乙酰胆碱受体激动剂。在提议的更新中要测试的假设是 DMXB-A 将为患有精神分裂症的退伍军人带来显着的神经认知改善。