Pharmacotherapy for Opiate Addiction and Toxicity

阿片成瘾和中毒的药物治疗

基本信息

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
项目类别：
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

项目摘要

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广泛用于治疗剧烈疼痛，但它们产生的成瘾性和副作用往往限制了它们的使用。这项研究的目标是开发一种基于内源性肽甘氨酰谷氨酰胺 (Gly-GIn) 的吗啡成瘾和毒性的新型治疗方法。 Gly-Gln 在大脑中由阿片肽、β-内啡肽合成。在临床前研究中，给实验动物施用 Gly-Gln 可预防吗啡引起的呼吸抑制和低血压，且不会影响吗啡缓解急性疼痛的能力。拟议的研究将测试 Gly-Gln 抑制吗啡成瘾、耐受性和依赖性的假设，并确定 Gly-Gln 是否影响慢性疼痛实验模型中的吗啡镇痛作用。目标 1 将扩展初步证据，证明 Gly-GIn 预处理可防止获得对吗啡的条件性位置偏好（一种药物成瘾动物模型，用于测量成瘾药物的奖赏或激励效果），并确定 Gly-GIn 是否也抑制奖赏效果尼古丁。目标 2 将继续进行初步研究，表明 Gly-GIn 预处理可抑制吗啡镇痛耐受性的产生，并降低身体依赖性的严重程度。目标 3 将测试 Gly-Gln 是否影响慢性神经性疼痛和炎性疼痛实验模型中的吗啡镇痛作用。我们期望发现 Gly-Gln 不会干扰吗啡对这些慢性疼痛的治疗，并进一步假设它可能产生有益的作用，即它可能会增强吗啡镇痛并减少疼痛过敏。拟议的商业应用：目前尚无有效的治疗方法吗啡成瘾和毒性不会影响吗啡缓解疼痛的能力。这开发一种消除阿片类药物奖励效应的化合物可能会为减少吗啡的滥用潜力提供一种务实的方法，并且选择性预防吗啡不良反应的能力将为遭受严重疼痛的患者带来显着的益处。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal.

甘氨酰谷氨酰胺是一种内源性 β-内啡肽衍生肽，可抑制吗啡诱导的条件性位置偏好、耐受性、依赖性和戒断。

DOI：
发表时间：
2005-11
期刊：
影响因子：
0
作者：
Cavun, Sinan;Goktalay, Gokhan;Millington, William R
通讯作者：
Millington, William R

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：
发表时间：
2006-01-13
期刊：
影响因子：
0
作者：
Goktalay, Gokhan;Cavun, Sinan;Levendusky, Mark C;Hamilton, Jonathan R;Millington, William R
通讯作者：
Millington, William R