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: 8167031
• 负责人: James Eisenach
• 金额: $ 0.69万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167031
• 关键词: Absence of pain sensation; Adrenergic Receptor; Alzheimer' s Disease; Cholinesterase Inhibitors; Cholinesterases; Clinical; 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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 基于实验室研究和我们对其作用机制的理解，两种批准用于治疗神经性疼痛的口服药物（加巴喷丁和度洛沙汀）和一种批准用于治疗痴呆症的口服药物（多奈哌齐）之间将存在深刻的积极相互作用，以治疗慢性疼痛患者。 这项研究是在神经性疼痛患者，并最终在一个定量的描述降去甲肾上腺素能活性，去甲肾上腺素转运体抑制剂，胆碱酯酶抑制剂的激活剂之间的相互作用，利用这种独特的可塑性镇痛慢性疼痛状态。我们不仅关注实验室研究中的机制假设，而且关注实际应用，使用临床批准的药物，包括加巴喷丁（Neurontin <$）激活去甲肾上腺素能活性，度洛沙汀（Cymbalta <$）抑制去甲肾上腺素转运蛋白，多奈哌齐（Aricept <$），批准用于治疗阿尔茨海默氏痴呆症，但以前没有测试过治疗神经性疼痛，抑制胆碱酯酶。这些药物中的每一种都可能通过除降向去甲肾上腺素能抑制以外的机制起作用，但我们假设它们组合的治疗强度在很大程度上依赖于由去甲肾上腺素能发芽和α 2-肾上腺素受体功能改变引起的级联反应。这项研究将为这一假设提供关键的检验和关键的信息，以指导更有效的神经病理性疼痛的临床治疗。