NITROUS OXIDE AND ENDORPHINS

一氧化二氮和内啡肽

• 批准号: 3220395
• 负责人: RAYMOND MARK QUOCK
• 金额: $ 6.05万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3220395
• 关键词: analgesics; drug addiction antagonist; high performance liquid chromatography; morphine; naloxone; neuropharmacology; neurotensin; nitrous oxide; perfusion; radioassay; vasopressins

Nitrous oxide is widely used clinically for conscious sedation and also in surgical anesthesia, however, the mechanism of its analgesic action has remained unknow. Other investigators have reported that nitrous oxide-induced analgesia is antagonized by the opiate receptor blocker naloxone and, in preliminary investigations, we have found that exposure to 75% nitrous oxide: 25% oxygen produces a reversible increase in the methionine-enkephalin (ME)-like immunoreactivity in fractions of artificial cerebrospinal fluid collected from ventricular-cisternally-perfused, anesthetized rats. Based upon these findings, we hypothesize that nitrous oxide can induce neuronal release of specific opioid peptides and that this drug action might be associated with the analgesic effect of nitrous oxide. Our specific aim is to submit this hypothesis to testing by a set of postulates designed to verify an opiate involvement in a physiological or pharmacological process. These tests will involve 1. antagonism by naloxone, 2. non-antagonism by (+)-naloxone, 3. cross-tolerance with morphine, 4. potentiation by inhibitors of enkephalin metabolism, and 5. demonstration of release of opioid peptides. These tests will be conducted, using nitrous oxide-induced analgesia in behavioral models and nitrous oxide-induced changes in perfusate ME-like immunoreactivity in anesthetized and conscious centrally-perfused rats. Our methods will include the rat tail flick test, the rat hot plate test, ventricular-cisternal perfusion, intrathecal perfusion, radioimmunoassay and high performance liquid chromatography separation or assay of opioid peptides. The long-term objectives of this research are to systemically analyze the drug actions and effects of nitrous oxide and eventually other general anesthetic drugs as well. The findings of this research should contribute to our understanding and knowledge of the pharmacology of nitrous oxide.

一氧化二氮在临床上广泛用于清醒镇静， 然而，外科麻醉，其镇痛作用的机制， 仍然不为人知。 其他研究人员报告说， 阿片受体阻滞剂可拮抗氧化诱导的镇痛作用 纳洛酮，在初步调查中，我们发现， 75%的一氧化二氮：25%的氧气产生可逆的增加， 甲硫氨酸-脑啡肽（ME）样免疫反应性的部分人工 从脑室脑池灌注收集脑脊液， 麻醉大鼠。 基于这些发现，我们假设， 氧化物可以诱导神经元释放特定的阿片肽， 药物作用可能与亚硝酸钠的镇痛作用有关 环氧 我们的具体目标是将这一假设提交给一组测试 旨在验证阿片类药物参与生理 或药理学过程。 这些测试将涉及1。 拮抗作用 纳洛酮，2. （+）-纳洛酮的非拮抗作用，3. 交叉耐受性 吗啡，4. 脑啡肽代谢抑制剂的增强作用，和5. 阿片肽释放的证明。 这些测试将 在行为模型中使用一氧化氮诱导的镇痛， 一氧化二氮诱导的灌流液ME样免疫反应性的变化， 麻醉和清醒的中枢灌注大鼠。 我们的方法将 包括大鼠甩尾试验，大鼠热板试验， 脑室-脑池灌注，鞘内灌注，放射免疫分析 以及阿片样物质的高效液相色谱分离或测定 缩氨酸 这项研究的长期目标是系统地 分析药物的作用和一氧化二氮的影响，并最终其他 全身麻醉药也一样。 这项研究的结果应该 有助于我们对药理学的理解和知识， 一氧化氮