TWIK-1/TREK-1-IN-1 (compound 2a) is an inhibitor of the TWIK-related potassium channel ( Potassium Channel ) TREK-1. TREK-1 contains a two-pore domain potassium (K2p) channel that dimerizes into TREK-1 homodimer and TWIK-1/TREK-1 heterodimer, and is an important antidepressant target. TWIK-1/TREK-1-IN-3 targets TREK-1 homodimer and TWIK-1/TREK-1 heterodimer with IC 50 s of 9.36 μM and 14.6 μM, respectively, and has antidepressant-like effects.