ENHANCEMENT OF OPIOID ANALGESIA IN HUMAN

增强人类阿片类镇痛作用

• 批准号: 3211912
• 负责人: HARLAN F HILL
• 金额: $ 26.69万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1994-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3211912
• 关键词: analgesics; cholecystokinin; desipramine; dosage; drug addiction; drug adverse effect; drug metabolism; fenfluramine; fentanyl; hormone inhibitor; opiate alkaloid

The long-term objective of this research is to improve clinical management of persistent pian states. The goal of the proposed work is to evaluate the ability for a norepinephrine re-uptake inhibitor and a serotonin releaser (desipramine and fenfluramine) to enhance human opioid analgesia. Analgesia effect measures will be derived from a human testing model based on painful tooth pulp stimulation: Subjective pain report, dental evoked potentials, and EEG measures will be obtained. The first stage in this work will address the hypothesis that desipramine and fenfluramins exert an analgesic effect when administered alone. The second stage of the work will evaluate the ability of these drugs to enhance opioid analgesia. To accomplish the latter we will administer the opioid alfentanil at three different plasma concentrations to normal volunteers using pharmacokinetically tailored infusions. These infusions will permit the evaluation of the effects of the candidates enhancers (also infuse at steady-state concentrations) while the subject is experiencing opioid analgesia at steady- state, We predict that neither of the candidate enhancers used above will demonstrated analgesic effects, but each of the enhancers when used in combination with the alfentanil infusion is predicted to increase opioid analgesia and alter the relationship of opioid side effects to plasma concentration. Finally, we will evaluate the effects of proglumide, a cholecystokinin antagonist, alone and in combination with alfentanil, on measures of analgesia. A model is proposed for the modulation of opioid analgesia in which norepinephrine and serotonin systems are balanced against the cholecystokinin system in an opponent process relationship.

这项研究的长期目标是改善临床 持续的钢琴国家的管理。 提议的目标 工作是评估去甲肾上腺素再摄取的能力 抑制剂和5-羟色胺释放蛋白（去甲胺和芬氟胺） 增强人类阿片类镇痛。 镇痛效应措施将 源自基于疼痛牙髓的人类测试模型 刺激：主观疼痛报告，牙齿诱发潜力和 将获得脑电图措施。 这项工作的第一阶段将 解决了去丙胺和芬氟胺作用的假设 单独给药时镇痛作用。 第二阶段 工作将评估这些药物增强阿片类药物的能力 镇痛。 为了完成后者，我们将管理阿片类药物 阿芬太尼以三种不同的血浆浓度为正常 使用药理量身定制的输注的志愿者。 这些 输注将允许评估 候选增强子（也以稳态浓度注入） 虽然受试者在稳定时经历阿片类镇痛 声明，我们预测候选增强剂都没有使用 以上将表现出镇痛作用，但每个 与阿尔芬太尼输注结合使用时，增强剂为 预计会增加阿片类镇痛并改变关系 阿片类药物对等离子体浓度的副作用。 最后，我们会的 评估Proglumide（胆囊动蛋白拮抗剂）的作用， 单独并与阿尔芬太尼（Alfentanil）结合使用，以镇痛度的措施。 提出了一个模型，以调节阿片类镇痛 去甲肾上腺素和5-羟色胺系统与 在对手过程关系中的胆囊动蛋白系统。