Kv7.2 and Kv7.3 are voltage-gated potassium channels subunits mainly expressed in neurons where they underlie the M-current (IKM), a sub-threshold K+ current controlling action potentials generation and frequency. The Kv7.2/7.3 channel opener retigabine is an antiseizures drug used until 2017 when it was withdrawn from the market for safety reasons. Since then, no Kv7 activator is currently available for clinical use. We used a drug repurposing strategy to identify novel Kv7.2/3 activators. A library of 5600 compounds, mostly represented by clinically-approved drugs, was screened in CHO cells stably-expressing Kv7.3 A315T channels, using a Thallium flux-based fluorescent assay. This variant increases current size, thus improving the signal/noise ratio of our assay. Among 12 confirmed hits, one (C4) showed potency and efficacy similar to that of retigabine for Kv7.3 A315T channel activation. Whole-cell patch-clamp studies revealed that C4 was slightly less potent and less effective than retigabine in activating Kv7.3 A315T channels. However, when tested in CHO cells expressing Kv7.2+Kv7.3 channels, retigabine and C4 showed similar efficacy (maximal ΔV1/2 was 38.9±3.6mV and 37.8±3.6mV for retigabine and C4, respectively) and potency (EC50s were 1.2±0.3µM and 2.5±1.8µM for retigabine and C4, respectively). Finally, C4 displayed significant anticonvulsant activity in two mouse seizure models: the pentylenetetrazol induced-seizures and the sound-induced seizures in DBA/2 mice. In both models, anticonvulsant ED50 values for C4 were comparable to those for retigabine. Upon pretreatment with the Kv7 blocker XE-991, C4 anticonvulsant effects were significantly reduced in both models, confirming that its antiseizures efficacy was Kv7-mediated.