DISPOSITION, METABOLISM & PROCESSING OF OPIATE AGONISTS, ANTAGONISTS & OPIOIDS

具体目标是：a.开发利用激光的新方法 解吸扩展范围质谱仪定性(和 随后，半定量或定量)确定 单一基因产物衍生的多种神经肽的存在 (例如前强啡肽和加工强啡肽A；前脑啡肽 和加工的脑啡肽；前阿片黑素皮质素(POMC)亲本 来源于POMC、促肾上腺皮质激素的多肽和多肽 促黑素细胞激素(MSH)的内啡肽(ACTH) 然后呢？-MSH)。B.使用这些新技术(单独或组合使用 用高效液相色谱法和/或放射免疫法)同时进行定性和/或 阿片肽和其他神经肽的定量分析 与内源性阿片系统有关(如促肾上腺皮质激素释放 凝血因子(CRF)、缩胆囊素(CCK)、P物质及其加工 多肽)。C.使用这些技术来研究 中枢神经递质活性水平的变化 内源性阿片类药物的处理(例如，水平改变的影响 多巴胺在强啡肽加工中的作用)。D.使用这些技术来 研究滥用药物和潜在的治疗药物对疾病的影响 阿片肽的加工和降解(如可卡因、吗啡和 乙醇效应；美沙酮、纳美芬和氟西汀效应)。近期 描述这项工作的论文如下：于俊杰，E.R.巴特尔曼， J.H.伍兹，B.T.Chait，M.J.Kreek《强啡肽A(1-8)模拟，E-2078， 在人和恒河猴血中是稳定的。 治疗学280(1997)1147-1151。于俊杰，E.R.巴特尔曼，J.H.伍兹， 强啡肽A(1-8)类似物，E2078 恒河猴血脑屏障>，《药学杂志》，第282页。 (1997)633-638。

The specific aims are A. To develop novel methods using laser desorption extended-range mass spectrometry to qualitatively (and subsequently, semi-quantitatively or quantitatively) determine the presence of multiple neuropeptides derived from a single gene product (e.g. prodynorphin and processed dynorphin A peptides; proenkephalin and processed enkephalin peptides; proopiomelanocortin (POMC) parent peptide and multiple peptides derived from POMC, adrenocorticotropin hormone (ACTH), ?-endorphin, of ?-melanocyte-stimulating hormone (MSH) and ?-MSH). B.To use these novel techniques (alone or in combination with HPLC and/or RIA) for the simultaneous qualitative and/or quantitative analysis of opioid peptides and other neuropeptides related to the endogenous opioid system (e.g. Corticotropin releasing factor (CRF), cholecystokinin (CCK), substance P and their processed peptides). C. To use these techniques in studies of the effects of alterations in levels of activity of neurotransmitters on the processing of endogenous opioids (e.g. the effects of altered levels of dopamine on dynorphin processing). D. To use these techniques to study the effects of drugs of abuse and potential treatment agents on opioid peptide processing and degradation (e.g. cocaine, morphine and ethanol effects; methadone, nalmefene and fluoxetine effects). Recent papers describing this work are listed below: J. Yu, E.R. Butleman, J.H. Woods, B.T. Chait, M.J. Kreek "Dynorphin A(1-8) Analog, E-2078, is stable in Human and Rhesus Monkey Blood" J. Pharm. Experimental Therapeutics 280 (1997) 1147-1151. J. Yu, E.R. Butleman, J.H. Woods, B.T. Chait, M.J. Kreek "Dynorphin A(1-8) analog, E2078, crosses the blood-brain barrier in rhesus monkeys" J. Pharmacol. Exp. Ther. 282 (1997) 633-638.