CLINICAL TRIAL: THREE WAY INTERACTION AMONG GABAPENTIN, DULOXETINE, AND DONEPEZI

临床试验：加巴喷丁、度洛西汀和多奈哌齐之间的三种相互作用

• 批准号: 7951406
• 负责人: James Eisenach
• 金额: $ 1.22万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7951406
• 关键词: Absence of pain sensation; Adrenergic Receptor; Alzheimer' s Disease; Aricept; Cholinesterase Inhibitors; Cholinesterases; Clinical; Clinical Research; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Dementia; Funding; Grant; Institution; Laboratory Study; Oral; Patients; Pharmaceutical Preparations; Research; Research Personnel; Resources; Source; Testing; Therapeutic; United States National Institutes of Health; base; chronic pain; donepezil; duloxetine; gabapentin; inhibitor/antagonist; noradrenaline transporter; noradrenergic; painful neuropathy; practical application

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Based on laboratory studies and our understanding of their mechanism of action, there will be a profound positive interaction between two oral drugs approved for the treatment of neuropathic pain (gabapentin and duloxetine) and an oral drug approved for treatment of dementia (donepezil) to treat patients with chronic pain. This study is in patients with neuropathic pain, and will culminate in a quantitative description of interactions between activators of descending noradrenergic activity, norepinephrine transporter inhibitors, and cholinesterase inhibitors to exploit this unique plasticity of analgesia in chronic pain states. We focus not only on mechanistic hypotheses in the laboratory studies, but also on practical applications, using clinically approved drugs, including gabapentin (Neurontin¿) to activate noradrenergic activity, duloxetine (Cymbalta¿) to inhibit the norepinephrine transporter, and donepezil (Aricept¿), approved for the treatment of Alzheimer s dementia, but not previously tested to treat neuropathic pain, to inhibit cholinesterase. Each of these drugs may act by mechanisms in addition to those involved in descending noradrenergic inhibition, but we hypothesize that the therapeutic strength of their combination relies heavily on this cascade engendered by noradrenergic sprouting and altered a2-adrenoceptor function. The proposed study will provide critical tests of this hypothesis and critical information to guide more effective clinical therapy of neuropathic pain.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 基于实验室研究及我们对其作用机制的理解，两种口服药物批准治疗神经性疼痛（加巴喷丁和杜洛西汀）和一种批准治疗痴呆症（Donepezil）治疗慢性疼痛患者的口服药物之间将存在深远的阳性相互作用。 这项研究是在神经性疼痛的患者中，将在降低甲肾上腺素活性，去甲肾上腺素转运蛋白抑制剂和胆碱酯酶抑制剂之间相互作用之间相互作用的定量描述中达到最终形式，以利用慢性疼痛状态的这种独特的镇痛可变性。我们不仅专注于实验室研究中的机理假设，还专注于使用临床批准的药物，包括加巴喷丁（神经素素）来激活去甲肾上腺素能活性，杜洛西汀（cymbalta¿），以抑制去甲肾上腺素的转运剂和DONEPEZIL（ARICEPT），无数的ALZHEIM deemer of Alzheimim of deemer，经治疗神经性疼痛的测试以抑制胆碱酯酶。这些药物中的每一种都可以通过机制来起作用，除了参与降甲肾上腺素能抑制的机制外，我们假设它们组合的治疗强度在很大程度上取决于甲肾上腺素能发芽并改变了A2-肾上腺素pecceptor的功能。拟议的研究将对这一假设和关键信息提供关键检验，以指导神经性疼痛的更有效的临床治疗。