Seredenin S B, Voronin M V
Eksp Klin Farmakol. 2009 Jan-Feb;72(1):3-11.
The interaction of afobazole (5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole dihydrochloride) and its main metabolite M-11 (2-[2-(3-oxomorpholine-4-yl)-ethylthio]-5-ethoxy benzimidazole hydrochloride) with neuroreceptors was studied using the method of radioligand analysis. The binding of afobazole with s1 (Ki =5.9 x 10(-6) M), MTI (Ki =1.6 x 10(-5) M), and MT3 (Ki =9.7 x 10(-7) M) receptors, as well as with a regulatory site of MAO-A (Ki = 3.6 x 10(-6) M) was revealed. The binding of M-11 with MT3 receptors (Ki = 3.9 x 10(-7) M) was demonstrated. The translocation of s1 receptor from endoplasmatic reticulum to the external membrane was revealed by the confocal microscopy technique on the immmortalized hippocampal HT-22 cells under the condition of 30- and 60-min-long afobazole (10(-8) M) application. Afobazole was shown to inhibit MAO-A reversibly. These properties of afobazole are consistent with our previous findings of the anxiolytic and neuroprotective effects of this drug.
采用放射性配体分析方法，研究了阿福唑（5-乙氧基-2-[2-(吗啉代)-乙硫基]苯并咪唑二盐酸盐）及其主要代谢产物M-11（2-[2-(3-氧代吗啉-4-基)-乙硫基]-5-乙氧基苯并咪唑盐酸盐）与神经受体的相互作用。结果显示，阿福唑与s1受体（Ki =5.9×10⁻⁶ M）、MTI受体（Ki =1.6×10⁻⁵ M）和MT3受体（Ki =9.7×10⁻⁷ M）以及单胺氧化酶A（MAO-A）的调节位点（Ki = 3.6×10⁻⁶ M）存在结合。证实了M-11与MT3受体（Ki = 3.9×10⁻⁷ M）有结合。在永生化海马HT-22细胞上，运用共聚焦显微镜技术，发现在应用30分钟和60分钟的阿福唑（10⁻⁸ M）条件下，s1受体从内质网向细胞膜外发生易位。结果表明，阿福唑可可逆性抑制MAO-A。阿福唑的这些特性与我们之前关于该药物抗焦虑和神经保护作用的研究结果一致。
