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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 基于实验室研究和我们对其作用机制的了解，两种被批准用于治疗神经性疼痛的口服药物(加巴喷丁和度洛西汀)与一种被批准用于治疗痴呆症的口服药物(多奈哌齐)将产生深刻的积极相互作用，用于治疗慢性疼痛患者。 这项研究是在神经病理性疼痛的患者中进行的，最终将对去甲肾上腺素能下行活性激活剂、去甲肾上腺素转运体抑制剂和胆碱酯酶抑制剂之间的相互作用进行定量描述，以开发慢性疼痛状态下这种独特的止痛可塑性。我们不仅关注实验室研究中的机械假说，还关注实际应用，使用临床批准的药物，包括激活去甲肾上腺素活性的加巴喷丁(Neurontin？)，抑制去甲肾上腺素转运体的度洛西汀(Cymbalta)，以及被批准用于治疗阿尔茨海默病S痴呆的多奈哌齐(Aricept)，但以前未经试验用于治疗神经性疼痛和抑制胆碱酯酶。这些药物中的每一种都可能通过与去甲肾上腺素能下行抑制相关的机制发挥作用，但我们假设，它们组合的治疗强度在很大程度上依赖于去甲肾上腺素能萌芽和改变2-肾上腺素受体功能所产生的级联反应。这项拟议的研究将提供对这一假说的关键检验和关键信息，以指导更有效的神经病理性疼痛的临床治疗。