Voronin Mikhail V, Kadnikov Ilya A
Department of Pharmacogenetics Federal State Budgetary Institution "Research Zakusov Institute of Pharmacology" Moscow Russia.
Pharmacol Res Perspect. 2016 Nov 7;4(6):e00273. doi: 10.1002/prp2.273. eCollection 2016 Dec.
Anxiolytic afobazole (5-Ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihidrochloride) has pronounced ligand properties toward Sigma-1 receptor (1 receptor,SigmaR1) and MT receptors. Our previous work demonstrated that afobazole possess cytoprotective effect in the in vitro model of menadione genotoxicity (Woods et al. 1997) through interaction with MT receptor (Kadnikov et al. 2014). Present study utilized previously described models to address the contribution of SigmaR1 to cytoprotective action of afobazole. The reduction in afobazole cytoprotective effect observed after preincubation of cell suspension with selective SigmaR1 antagonist BD-1047 revealed an important contribution of SigmaR1 in afobazole-mediated effect. We confirmed our observation using selective SigmaR1 agonist PRE-084. We conclude that pronounced cytoprotective effect of afobazole over PRE-084 is likely achieved by additive SigmaR1 and MT -mediated effects.
抗焦虑药阿福唑（5-乙氧基-2-[2-(吗啉代)乙硫基]苯并咪唑二盐酸盐）对西格玛-1受体（1型受体，SigmaR1）和褪黑素（MT）受体具有显著的配体特性。我们之前的研究表明，阿福唑通过与MT受体相互作用，在维生素K3遗传毒性的体外模型中具有细胞保护作用（伍兹等人，1997年）（卡德尼科夫等人，2014年）。本研究利用先前描述的模型来探讨SigmaR1对阿福唑细胞保护作用的贡献。在用选择性SigmaR1拮抗剂BD-1047预孵育细胞悬液后，观察到阿福唑细胞保护作用降低，这揭示了SigmaR1在阿福唑介导的效应中的重要作用。我们使用选择性SigmaR1激动剂PRE-084证实了我们的观察结果。我们得出结论，阿福唑比PRE-084具有更显著的细胞保护作用，这可能是通过SigmaR1和MT介导的相加效应实现的。
