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的疼痛，但产生的成瘾和副作用通常会限制其使用。这项研究的目的是基于内源性肽，糖基谷氨酰胺（Gly-GIN）开发一种新型吗啡成瘾和毒性的治疗方法。 Gly-gin是通过阿片类肽β-内啡肽在大脑中合成的。在临床前研究中，对实验动物的Gly-GIN给药可阻止吗啡引起的呼吸抑郁和低血压，而不会损害吗啡的缓解急性疼痛的能力。拟议的研究将检验以下假设，即在慢性疼痛的实验模型中，Gly吉金抑制吗啡成瘾，耐受性和依赖性，并确定Gly-Gin是否影响吗啡镇痛。 AIM 1将扩展初步证据，表明Gly-GIN预处理可防止获得条件地位偏爱吗啡的偏好，这是一种衡量成瘾药物的奖励或激励作用的药物成瘾模型，并确定Gly-GIN是否还抑制了Nicotine的奖励作用。 AIM 2将继续进行初步研究，表明Gly-GIN预处理抑制了对吗啡镇痛的耐受性的发展，并降低了身体依赖的严重程度。 AIM 3将测试Gly-Gin在慢性神经性和炎症性疼痛的实验模型中是否影响吗啡镇痛。我们希望发现Gly-GIN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会产生有益的作用，它可能会增强吗啡镇痛并降低疼痛超敏反应。 拟议的商业应用：目前，没有有效的治疗方法 吗啡成瘾和毒性不会干扰吗啡缓解疼痛的能力。这 消除鸦片制剂的奖励作用的化合物的开发可能会提供一种务实的方法来减少吗啡的滥用潜力，并且有选择地预防吗啡的不良反应的能力对患有严重疼痛的患者有重大好处。

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