Interaction of 2-mercaptobenzimidazole derivatives with sigma-1 receptors

The interaction of afobazole and its main metabolite M-11 {2-[2-(3-oxomorpholin-4-yl)ethylthio]-5-ethoxybenzimidazole hydrochloride} with sigma-1 (sigma(1)) receptors was studied in vitro in radioligand binding experiments on human T-cell lymphoblast-like cell line. Afobazole exhibited ligand properties towards sigma(1) receptors with IC50 = 7.1 x 10(-6) M. For M-11, the corresponding value was IC50 = 9.6x10(-4) M. Experiments in vitro on CD-1 mouse brain homogenate established that afobazole interacted with sigma(1) receptors (IC50 = 1.37x10(-5) M) whereas M-11 did not show affinity towards sigma(1) receptors (IC50 > 5x10(-4) M). Radioligand analysis results on mongrel CD-1 mice confirmed the results obtained on human T-cell lymphoblast-like cell line and led to the conclusion that sigma(1) receptors did not contribute to the pharmacological effects of M-11.