Spadin is a natural peptide released from the maturation of neurotensin receptor 3 (also known as sortilin) which acts as a TREK-1 (TWIK-related K+ channel-1) channel blocker with an IC50 of 71 nM. In electrophysiological studies, spadin blocks the TREK-1 activity in COS-7 cells, in cultured hippocampal pyramidal neurons and CA3 hippocampal neurons in brain slices and in vivo induces an increase of the 5-HT neuron firing rate in the dorsal raphe nucleus. Spadin is brain penetrant, and exhibits antidepressant effects in mouse models of depression with a rapid onset of action and an absence of adverse effects. The antidepressant properties are associated with increased neurogenesis and synaptogenesis in the brain.
