Neuropharmacology of Tramadol: Clinical Efficacy and Abuse Potential

曲马多的神经药理学：临床疗效和滥用潜力

• 批准号: 7729609
• 负责人: William Walton Stoops
• 金额: $ 58.15万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7729609
• 关键词: Agonist; American; Analgesics; Animals; Basic Science; Behavioral; Clinical; Cocaine; Data; Development; Disease; Dose; Double-Blind Method; Drug usage; Enrollment; Future; Health; Heroin; Human; Human Volunteers; Hydrocodone; Hydromorphone; Individual; Knowledge; Marijuana; Measures; Mediating; Methamphetamine; Naltrexone; Neuropharmacology; Neurotransmitters; Norepinephrine; Norepinephrine Receptors; Opioid; Opioid Analgesics; Oxycodone; Performance; Pharmaceutical Preparations; Pharmacology; Physical Dependence; Physicians; Physiological; Placebo Control; Placebos; Prevalence; Procedures; Public Health; Randomized; Relative (related person); Reporting; Research; Rewards; Role; Serotonin; Stimulus; Surveys; System; Testing; Time; Tramadol; United States; aged; clinical efficacy; mu opioid receptors; noradrenergic; norepinephrine system; novel; opioid abuse; opioid misuse; opioid withdrawal; public health relevance; research study; reuptake; tramadol abuse; volunteer

DESCRIPTION (provided by applicant): Prescription opioid misuse and abuse are increasing problems in the United States. In the 2006 National Survey on Drug Use and Health, 5.2 million Americans had illicitly used a prescription opioid in the past month. National rates of illicit prescription opioid use are higher than those for heroin, cocaine or methamphetamine and are exceeded only by marijuana. Moreover, the number of individuals initiating illicit use of prescription opioids was greater than that for marijuana in 2004 and 2005. These findings indicate that illicit prescription opioid use represents a significant public health concern greater than that of cocaine, heroin or methamphetamine and perhaps approaching that of marijuana. The increase in illicit prescription opioid use may be due to increased availability of opioid analgesics medications with significant abuse potential. Discovery and development of opioid analgesics with reduced abuse potential may serve to decrease prescription opioid misuse and the subsequent development of opioid use disorders. Tramadol is an unscheduled atypical analgesic with opioid activity. While rare cases of tramadol abuse and physical dependence have been reported, it has reduced abuse potential relative to typical prescription opioids. The reduced abuse potential of tramadol has been attributed to its novel pharmacology. Tramadol is a mu opioid agonist, but also blocks reuptake of serotonin and norepinephrine. The specific aim of the present application is to elucidate the relative contributions of mu opioid, serotonin and norepinephrine receptor systems to the effects of tramadol using an array of pharmacologic measures relevant to its abuse potential and analgesic efficacy in human volunteers. The knowledge gained about tramadol from the proposed experiments in terms of its neuropharmacology will aid in the discovery and development of other opioid medications with reduced abuse potential. Specifically, if the non-mu mediated effects of tramadol contribute to its analgesic efficacy and reduced abuse potential, these findings would support the development of other analgesics with similar neuropharmacological mechanisms. This project will employ placebo-controlled, randomized and double blind testing procedures to evaluate the behavioral effects of tramadol across three experiments. Overall, this project will contribute important clinical information regarding the pharmacology of tramadol in relation to its analgesic efficacy and reduced abuse potential and provide basic science information about the behavioral effects of prescription opioids in humans. PUBLIC HEALTH RELEVANCE: The research proposed in this application seeks to understand better the human neuropharmacology of tramadol, an atypical analgesic with opioid action that has reduced abuse potential relative to other opioid analgesics. We are seeking to understand how the neuropharmacology of tramadol influences both its analgesic efficacy and reduced abuse potential in an effort to aid development of other analgesic medications with reduced abuse potential. Developing analgesics with reduced abuse potential may reduce the prevalence of prescription opioid misuse and subsequent opioid use disorders.

描述(由申请人提供)：处方阿片类药物的滥用和滥用在美国越来越多的问题。在2006年全国药物使用与健康调查中，520万美国人在过去的一个月里非法使用了处方阿片类药物。全国非法处方阿片类药物的使用率高于海洛因、可卡因或甲基苯丙胺，只有大麻超过。此外，在2004年和2005年，开始非法使用处方类阿片的人数超过了使用大麻的人数。这些发现表明，非法处方阿片类药物的使用是一个重大的公共卫生问题，比可卡因、海洛因或甲基苯丙胺更大，甚至可能接近大麻。非法处方阿片类药物使用增加的原因可能是具有显著滥用潜力的阿片类止痛药的供应增加。发现和开发减少滥用潜力的阿片类止痛药可能有助于减少处方阿片类药物的滥用和随后阿片类药物使用障碍的发展。曲马多是一种非程序非典型止痛药，具有阿片类活性。虽然报告了罕见的曲马多滥用和身体依赖病例，但与典型的处方阿片类药物相比，它减少了滥用的可能性。曲马多滥用潜力的减少归因于其新颖的药理作用。曲马多是一种u阿片类激动剂，但也能阻止5-羟色胺和去甲肾上腺素的再摄取。本申请的具体目的是利用一系列与曲马多在人体内的滥用潜力和止痛效果相关的药理学措施，阐明u阿片类药物、5-羟色胺和去甲肾上腺素受体系统对曲马多作用的相对贡献。从拟议的实验中获得的关于曲马多的神经药理学方面的知识将有助于发现和开发其他减少滥用潜力的阿片类药物。具体地说，如果曲马多的非MU中介效应有助于其止痛效果和减少滥用潜力，这些发现将支持其他具有类似神经药理机制的止痛药的开发。该项目将使用安慰剂对照、随机和双盲测试程序来评估曲马多在三个实验中的行为效果。总体而言，该项目将为曲马多的止痛疗效和减少滥用潜力的药理学提供重要的临床信息，并提供有关处方阿片类药物对人类行为影响的基本科学信息。公共卫生相关性：本申请中提出的研究旨在更好地了解曲马多的人类神经药理学，曲马多是一种具有阿片类药物作用的非典型止痛药，与其他阿片类止痛药相比，它减少了滥用的可能性。我们正在努力了解曲马多的神经药理学如何影响其镇痛效果和减少滥用潜力，以努力帮助开发其他减少滥用潜力的止痛药。开发减少滥用潜力的镇痛剂可能会减少处方阿片类药物滥用和随后的阿片类药物使用障碍的流行率。