Synergistic inhibition of butyrylcholinesterase by galantamine and citalopram.
Synergistic inhibition of butyrylcholinesterase by galantamine and citalopram.
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DOI：
10.1016/j.bbagen.2011.08.010
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发表时间：
2011-12
影响因子：
3
通讯作者：
Darvesh, Sultan
中科院分区：
文献类型：
--
作者：
Walsh, Ryan;Rockwood, Kenneth;Martin, Earl;Darvesh, Sultan
关键词：
许多接受加兰他敏治疗的阿尔茨海默病（AD）患者似乎从西酞普兰中获得了额外的认知益处。两种药物均抑制乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）。这些酶共同调节乙酰胆碱催化剂。在AD脑中，AChE减少，而BuChE没有，这表明BuChE抑制可能在提高乙酰胆碱水平中很重要。BuChE在突触间隙达到高乙酰胆碱水平时会被激活。本研究探索了一种联合加兰他敏和西酞普兰治疗AD的方法。分光光度法研究的BuChE催化加兰他敏或西酞普兰或两者的存在或不存在下，使用Ellman方法进行。数据分析涉及扩展我们以前的方程描述BuChE催化。加兰他敏在低底物浓度下（VS = 42.0 μM/min; VS（gal）= 0）完全抑制BuChE，而不影响酶的底物活化形式（VSS = VSS（gal）= 62.3 μM/min）。相反，西酞普兰抑制未活化（VS = 42.0 μM/min; VS（cit）= 6.75 μM/min）和底物活化（VSS = 62.3 μM/min; VSS（cit）= 45.2 μM/min）形式的BuChE。加兰他敏和西酞普兰联合使用可增加对未活化BuChE（VS = 42.0 μM/min; VS（gal）（cit）= 0.85 μM/min）和底物活化形式BuChE（VSS = 62.3 μM/min; VSS（gal）（cit）= 45.0 μM/min）的抑制。西酞普兰和加兰他敏对BuChE产生联合抑制作用，被认为具有协同作用。加兰他敏和西酞普兰联合给药的临床获益可能与BuChE的协同抑制作用有关，促进胆碱能神经传递。这强调了进一步研究药物组合在AD治疗中的重要性。
Many persons with Alzheimer’s disease (AD) treated with galantamine appear to receive additional cognitive benefit from citalopram. Both drugs inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These enzymes co-regulate acetylcholine catabolism. In AD brain, AChE is diminished while BuChE is not, suggesting BuChE inhibition may be important in raising acetylcholine levels. BuChE is subject to activation at high acetylcholine levels reached at the synaptic cleft. The present study explores one way combining galantamine and citalopram could be beneficial in AD. Spectrophotometric studies of BuChE catalysis in the absence or presence of galantamine or citalopram or both, were performed using the Ellman method. Data analysis involved expansion of our previous equation describing BuChE catalysis. Galantamine completely inhibited BuChE at low substrate concentrations (VS = 42.0 μM/min; VS(gal) = 0) without influencing the substrate-activated form of the enzyme (VSS = VSS(gal) = 62.3 μM/min). Conversely, citalopram inhibited both un-activated (VS = 42.0 μM/min; VS(cit) = 6.75 μM/min) and substrate-activated (VSS = 62.3 μM/min; VSS(cit) = 45.2 μM/min) forms of BuChE. Combined galantamine and citalopram increased inhibition of un-activated BuChE (VS = 42.0 μM/min; VS(gal)(cit) = 0.85 μM/min) and substrate-activated form (VSS = 62.3 μM/min; VSS(gal)(cit) = 45.0 μM/min). Citalopram and galantamine produce a combined inhibition of BuChE considered to be synergistic. Clinical benefit from combined galantamine and citalopram may be related to a synergistic inhibition of BuChE, facilitating cholinergic neurotransmission. This emphasizes the importance of further study into use of drug combinations in AD treatment.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
14.5
作者：
Smith, Gwenn S.;Kramer, Elisse;Eidelberg, David
通讯作者：
Eidelberg, David
影响因子：
6.1
作者：
Mesulam, M;Guillozet, A;Quinn, B
通讯作者：
Quinn, B
影响因子：
2.1
作者：
Darvesh, S;Walsh, R;Martin, E
通讯作者：
Martin, E
DOI：
10.1016/j.amjopharm.2011.02.003
发表时间：
2011-02-01
期刊：
AMERICAN JOURNAL OF GERIATRIC PHARMACOTHERAPY
影响因子：
--
作者：
Rockwood, Kenneth;Walsh, Ryan;Darvesh, Sultan
通讯作者：
Darvesh, Sultan