Institute of Organic Chemistry, Department of Chemistry and Pharmacy, University of Regensburg, 93053, Regensburg, Germany.
INSERM, INS, Institut de Neurosciences des Systèmes, Aix-Marseille University, 13005, Marseille, France.
Chemistry. 2020 Oct 6;26(56):12722-12727. doi: 10.1002/chem.202000710. Epub 2020 Sep 11.
Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABA Rs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition.
光遗传学和光药理学工具在操纵神经元抑制方面的效果和可逆性有限。我们报告了 Fulgazepam 的设计、合成和生物学评估，它是苯二氮䓬类药物的富里酰胺衍生物，表现为离子型 γ-氨基丁酸受体 (GABA Rs) 的纯增效剂，并在体外和体内具有完全和可逆的光开关。该化合物能够实现 GABA 能神经传递的高分辨率研究，以及基于局部、急性和可逆神经抑制的光疗。
