Pharmacotherapy for Opiate Addiction and Toxicity

阿片成瘾和中毒的药物治疗

• 批准号: 6786458
• 负责人: WILLIAM R MILLINGTON
• 金额: $ 10万
• 依托单位: ION TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786458
• 关键词: analgesia; analgesics; behavior test; behavioral /social science research tag; biotherapeutic agent; chemoprevention; chronic pain; drug abuse chemotherapy; drug abuse prevention; drug addiction; drug adverse effect; drug design /synthesis /production; drug screening /evaluation; drug tolerance; endorphins; glutamine; hypotension; inflammation; laboratory rat; morphine; naloxone; nervous system disorder; nicotine; reinforcer; respiratory disorder

DESCRIPTION (provided by applicant): Morphine and other opiate drugs are widely used to treat severe pain but the addiction and side effects they produce often limit their use. The goal of this research is to develop a novel treatment for morphine addiction and toxicity based on an endogenous peptide, glycyl-glutamine (Gly-GIn). Gly-GIn is synthesized in brain from the opioid peptide, beta-endorphin. In preclinical studies, Gly-GIn administration to laboratory animals prevented the respiratory depression and hypotension caused by morphine without compromising morphine's ability to relieve acute pain. The proposed research will test the hypothesis that Gly-GIn inhibits morphine addiction, tolerance and dependence and determine if Gly-GIn influences morphine analgesia in experimental models of chronic pain. Aim 1 will extend preliminary evidence that Gly-GIn pretreatment prevents the acquisition of a conditioned place preference to morphine, an animal model of drug addiction that measures the rewarding or incentive effect of addictive drugs, and determine if Gly-GIn also inhibits the rewarding effects of nicotine. Aim 2 will continue preliminary studies showing that Gly-GIn pretreatment inhibits development of tolerance to morphine analgesia and reduces the severity of physical dependence. Aim 3 will test whether Gly-GIn influences morphine analgesia in experimental models of chronic neuropathic and inflammatory pain. We expect to find that Gly-GIn does not interfere with morphine therapy for these chronic pain conditions and further hypothesize that it may produce beneficial effects, that it may potentiate morphine analgesia and reduce pain hypersensitivity. PROPOSED COMMERCIAL APPLICATION: At present, there are no effective treatments for morphine addiction and toxicity that do not interfere with morphine's ability to relieve pain. The development of a compound that nullifies the rewarding effects of opiates may provide a pragmatic approach for reducing morphine's abuse potential and the ability to selectively prevent morphine's adverse effects would be of significant benefit to patients suffering severe pain.

描述（由申请人提供）：吗啡和其他阿片类药物被广泛用于治疗严重疼痛，但它们产生的成瘾性和副作用往往限制了它们的使用。本研究的目的是开发一种基于内源性肽甘氨酰谷氨酰胺（Gly-Gln）的吗啡成瘾和毒性的新治疗方法。Gly-Gln在大脑中由阿片肽β-内啡肽合成。在临床前研究中，对实验室动物施用Gly-Gln防止了由吗啡引起的呼吸抑制和低血压，而不损害吗啡缓解急性疼痛的能力。这项研究将检验Gly-Gln抑制吗啡成瘾、耐受和依赖的假设，并确定Gly-Gln是否影响慢性疼痛实验模型中的吗啡镇痛。目的1将扩大初步证据表明，甘氨酸-GIn预处理防止收购的条件性位置偏好吗啡，药物成瘾的动物模型，衡量成瘾药物的奖励或激励作用，并确定如果甘氨酸-GIn也抑制尼古丁的奖励作用。目标2将继续初步研究表明，Gly-Gln预处理抑制吗啡镇痛耐受的发展，并降低身体依赖的严重程度。目的3将测试Gly-Gln是否影响慢性神经病理性疼痛和炎症性疼痛实验模型中的吗啡镇痛。我们期望发现Gly-Gln不会干扰这些慢性疼痛状况的吗啡治疗，并进一步假设它可能产生有益的效果，它可能增强吗啡镇痛并降低疼痛超敏性。 拟议商业应用：目前尚无有效的治疗方法 吗啡成瘾和毒性，不干扰吗啡的止痛能力。的 开发一种消除阿片类药物的奖励作用的化合物可以提供一种减少吗啡滥用可能性的实用方法，并且选择性地预防吗啡副作用的能力将对遭受严重疼痛的患者具有显著的益处。

项目成果

Glycyl-glutamine inhibits nicotine conditioned place preference and withdrawal.

甘氨酰谷氨酰胺抑制尼古丁条件性位置偏好和戒断。

• DOI: 10.1016/j.ejphar.2005.11.034
• 发表时间: 2006
• 期刊: European journal of pharmacology.
• 作者: Goktalay,Gokhan;Cavun,Sinan;Levendusky,MarkC;Hamilton,JonathanR;Millington,WilliamR
• 通讯作者: Millington,WilliamR