Tipepidine hydrochloride reversibly inhibits dopamine (DA) D2 receptor-mediated GIRK currents (IDA(GIRK)) with an IC50 of 7.0 μM. Tipepidine hydrochloride subsequently activates VTA dopamine neuron. Tipepidine hydrochloride, a non-narcotic antitussive, exerts an antidepressant-like effect.