In vitro toxicity of the galanin receptor 3 antagonist SNAP 37889

Abstract Galanin and its receptors (GAL 1 , GAL 2 , GAL 3 ) modulate a range of neuronal, immune and vascular activities. In vivo administration of SNAP 37889 (1-phenyl-3-[[3-(trifluoromethyl)phenyl]imino]-1H-indol-2-one), a potent small non-peptidergic antagonist of GAL 3 , was reported to reduce anxiety- and depression-related behavior, ethanol consumption, and antagonizes the effect of galanin on plasma extravasation in rodent models. Accordingly, SNAP 37889 has been proposed as a potential therapeutic agent to treat anxiety and depression disorders. Therefore, we evaluated the toxicity of SNAP 37889 to different cell types. Our experiments revealed that SNAP 37889 (≥10μM) induced apoptosis in epithelial (HMCB) and microglial (BV-2) cell lines expressing endogenous GAL 3 , in peripheral blood mononuclear cells and promyelocytic leukemia cells (HL-60) expressing GAL 2 , and in a neuronal cell line (SH-SY5Y) lacking galanin receptor expression altogether. In conclusion, SNAP 37889 is toxic to a variety of cell types independent of GAL 3 expression. We caution that the clinical use of SNAP 37889 at doses that might be used to treat anxiety- or depression- related diseases could have unexpected non-galanin receptor-mediated toxicity, especially on immune cells.