Amoxapine displays a selective inhibition of GLYT2a behaving as a 10 fold more efficient inhibitor of this isoform than of GLYT1b in human embryonic kidney 293 cells. Amoxapine behaves as a competitive inhibitor of both glycine and chloride and a mixed-type inhibitor with respect to sodium. Amoxapine causes acute hERG blockade in oocytes with IC50 of 21.6 mM and in HEK 293 cells with IC50 of 5.1 mM. Amoxapine block is reverse frequency-dependent and causes accelerated and leftward-shifted inactivation. Amoxapine application results in chronic reduction of hERG trafficking into the cell surface membrane with IC50 of 15.3 mM in HEK 293 cells.