Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.
Allosteric modulation of seven transmembrane spanning receptors: theory, practice, and opportunities for central nervous system drug discovery.
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DOI：
10.1021/jm201139r
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发表时间：
2012-02-23
影响因子：
7.3
通讯作者：
Lindsley, Craig W.
中科院分区：
文献类型：
--
作者：
Melancon, Bruce J.;Hopkins, Corey R.;Wood, Michael R.;Emmitte, Kyle A.;Niswender, Colleen M.;Christopoulos, Arthur;Conn, P. Jeffrey;Lindsley, Craig W.
负变构调节剂（NAMs），其降低通道活性并调节这些gaba能受体的能力，从而引发镇静、催眠和抗焦虑作用。除了PAMs和NAMs外，沉默变构调节剂（SAMs，或中性变构配体）在变构位点结合，可以阻断PAMs和NAMs的活性，但重要的是对正构配体反应没有影响。与直接作用GABAA激动剂的潜在致命影响相反，苯二氮卓类药物对GABAA的变构调节在临床上已被证明是安全有效的。4,9随着分子药理学和筛选技术的进步，目前已开发出其他离子通道、激酶、磷脂酶和7种跨膜跨越受体（7TMRs）的变构调节剂，也称为g蛋白偶联受体
(PAMs), which potentiate GABAA receptor response, and negative allosteric modulators (NAMs), which decrease channel activity and modulate the ability of these GABAergic receptors to elicit sedative, hypnotic, and anxiolytic effects. In addition to PAMs and NAMs, silent allosteric modulators (SAMs, or neutral allosteric ligands) bind at allosteric sites and can block the activity of PAMs and NAMs but importantly have no effect on orthosteric ligand responses. In contrast to the potentially deadly effects of direct acting GABAA agonists, allosteric modulation of GABAA by the benzodiazepine class has proven to be clinically safe and effective. 4, 9 With advances in molecular pharmacology and screening technology, allosteric modulators have now been developed for other ion channels, kinases, phospholipases and seven transmembrane spanning receptors (7TMRs, also known as G-protein-coupled receptors
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DOI：
10.1038/nrd2760
发表时间：
2009-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.5
作者：
Aurelio, Luigi;Valant, Celine;Scammells, Peter J.
通讯作者：
Scammells, Peter J.
影响因子：
64.8
作者：
Choe, Hui-Woog;Kim, Yong Ju;Ernst, Oliver P.
通讯作者：
Ernst, Oliver P.
影响因子：
7.3
作者：
Chen, C;Wilcoxen, KM;Grigoriadis, DE
通讯作者：
Grigoriadis, DE
影响因子：
7.3
作者：
Aurelio, Luigi;Valant, Celine;Scammells, Peter J.
通讯作者：
Scammells, Peter J.