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JAMA:猝睡症药物会影响脑中的多巴胺活性
[第1楼 PID5310] 2009-04-04 20:45 Sunset 写道:
JAMA:猝睡症药物会影响脑中的多巴胺活性
在健康男性中的初步研究提示,猝睡症药物modafinil(或译:莫达非尼)正越来越多地被用于改善认知能力。该药会影响多巴胺在脑中的活性,而其影响的方式可能会导致服用者对其的滥用和依赖性。以下是被引用的内容:来源:EurekAlert! 2009.03.19
Modafinil是一种促进清醒的药物,人们用它来治疗睡眠性的疾病。该药可能会增进认知的功能,并作为一种非标签指针用于对某些精神疾病(如精神分裂症、注意力缺失/过动症 [ADHD] )的认知功能障碍的治疗。根据文章的背景资料,Physicians’ Desk Reference 告诫说,该药可能会产生精神活性及欣快感的效应,这些都是中枢神经系统刺激性药物的典型药效。人们对这种药物被滥用的可能性存在着争议。人们对 Modafinil的作用机制并不十分了解,但被认为与那些精神刺激药物(如利他灵和安非他命)的作用机制不同,因为那些药物会通过标靶多巴胺转运蛋白而增加脑中的多巴胺(这是脑中的一种神经递质,它对中枢神经系统的正常功能是不可或缺的),这种机制是造成这些药物可能被滥用的基础。
National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md.的Nora D. Volkow, M.D.及其在Brookhaven National Laboratory的同僚开展了一项研究,旨在测试Modafinil在治疗剂量的时候是否会通过阻断多巴胺转运蛋白而增加脑中细胞外(即位于细胞外,或发生在细胞外的)的多巴胺含量。在该项研究中共有10位健康的男性,他们的年龄在23-46岁之间,他们或者服用安慰剂或是200毫克的 Modafinil(建议用来治疗猝睡症的剂量)或是400毫克的Modafinil(该剂量显示对治疗ADHD具有裨益)。Modafinil对细胞外多巴胺及对多巴胺转运蛋白的影响是用正电子发射断层扫描术(一种用来检验组织生物化学活性的放射学技术)来估测的。
研究人员发现:“在这一试点研究中,Modafinil能剧烈地增加人脑中的多巴胺的水平并阻断多巴胺转运蛋白。由于增加多巴胺的药物具有被滥用的可能性,并有鉴于Modafinil用于多种目的用途的增加,这些结果提示,该药物在敏感人中引起成瘾性的风险值得人们高度关注。”
Modafinil还会增加伏隔核中的多巴胺,这是一个被滥用药物产生奖励效应的一个关键性的脑区域。
对Modafinil的研发的期望是它会成为一种用于促进清醒的非多巴胺能标靶的药物。但是,目前在人体中的发现,加上临床前的研究证明了 Modafinil的促进清醒的效应中多巴胺起着不可或缺的作用,从而表明Modafinil的治疗作用机制是它具有能够增加多巴胺的作用。
出处:http://www.bioon.com/biology/biomed/387458.shtml
[第2楼 PID5310] 2012-08-20 19:27 Robot :
JAMA:猝睡症药物会影响脑中的多巴胺活性 相关
[第3楼 PID5311] 2009-04-04 20:46 Sunset 写道:
JAMA:猝睡症药物会影响脑中的多巴胺活性(英文原文)
Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human BrainClinical Implications
Nora D. Volkow, MD; Joanna S. Fowler, PhD; Jean Logan, PhD; David Alexoff, BSE; Wei Zhu, PhD; Frank Telang, MD; Gene-Jack Wang, MD; Millard Jayne, RN; Jacob M. Hooker, PhD; Christopher Wong, BA; Barbara Hubbard, RN; Pauline Carter, RN; Donald Warner, AA; Payton King, BA; Colleen Shea, MS; Youwen Xu, MS; Lisa Muench, BA; Karen Apelskog-Torres, AA
Context Modafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise.
Objective To measure the acute effects of modafinil at doses used therapeutically (200 mg and 400 mg given orally) on extracellular dopamine and on dopamine transporters in the male human brain.
Design, Setting, and Participants Positron emission tomography with [11C]raclopride (D2 / D3 radioligand sensitive to changes in endogenous dopamine) and [11C]cocaine (dopamine transporter radioligand) was used to measure the effects of modafinil on extracellular dopamine and on dopamine transporters in 10 healthy male participants. The study took place over an 8-month period (2007-2008) at Brookhaven National Laboratory.
Main Outcome Measures Primary outcomes were changes in dopamine D2 / D3 receptor and dopamine transporter availability (measured by changes in binding potential) after modafinil when compared with after placebo.
Results Modafinil decreased mean (SD) [11C]raclopride binding potential in caudate (6.1% [6.5%]; 95% confidence interval [CI], 1.5% to 10.8%; P = .02), putamen (6.7% [4.9%]; 95% CI, 3.2% to 10.3%; P = .002), and nucleus accumbens (19.4% [20%]; 95% CI, 5% to 35%; P = .02), reflecting increases in extracellular dopamine. Modafinil also decreased [11C]cocaine binding potential in caudate (53.8% [13.8%]; 95% CI, 43.9% to 63.6%; P < .001), putamen (47.2% [11.4%]; 95% CI, 39.1% to 55.4%; P < .001), and nucleus accumbens (39.3% [10%]; 95% CI, 30% to 49%; P = .001), reflecting occupancy of dopamine transporters.
Conclusions In this pilot study, modafinil blocked dopamine transporters and increased dopamine in the human brain (including the nucleus accumbens). Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.