通过 fomocaine 的偶氮化开发新型光致变色离子通道阻断剂。
Development of a new photochromic ion channel blocker via azologization of fomocaine.
机构信息
Department of Chemistry, Ludwig-Maximilians-Universität München , Munich 81377, Germany.
出版信息
ACS Chem Neurosci. 2014 Jul 16;5(7):514-8. doi: 10.1021/cn500070w. Epub 2014 Jun 5.
Abstract
Photochromic blockers of voltage gated ion channels are powerful tools for the control of neuronal systems with high spatial and temporal precision. We now introduce fotocaine, a new type of photochromic channel blocker based on the long-lasting anesthetic fomocaine. Fotocaine is readily taken up by neurons in brain slices and enables the optical control of action potential firing by switching between 350 and 450 nm light. It also provides an instructive example for "azologization", that is, the systematic conversion of an established drug into a photoswitchable one.
摘要
光致变色型电压门控离子通道阻断剂是用于精确控制神经元系统的有力工具，具有高时空分辨率的特点。我们现在介绍一种新型的光致变色型通道阻断剂 fotocaine，它基于长效麻醉剂 fomocaine。Fotocaine 很容易被脑片神经元摄取，并可通过在 350nm 和 450nm 光之间切换来实现动作电位发放的光控。它还为“azologization”提供了一个有启发性的范例，即系统地将一种已建立的药物转化为光致变色药物。
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2
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3
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Eur J Pharmacol. 2013 May 15;708(1-3):105-12. doi: 10.1016/j.ejphar.2013.03.001. Epub 2013 Mar 13.
4
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10
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