BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: KEY RESULTS: ONO-2506 inhibited spontaneous epileptic discharges in Cacna1a mice without affecting MES or PTZ. Given systemically, ONO-2506 increased basal release of GABA and kynurenic acid in the mPFC through activation of both neuronal and glial exocytosis, but inhibited depolarization-induced releases of all transmitters. ONO-2506 increased basal glial release of kynurenic acid without affecting those of L-glutamate, D-serine or GABA. However, ONO-2506 inhibited AMPA-induced releases of L-glutamate, D-serine, GABA and kynurenic acid. CONCLUSIONS AND IMPLICATIONS: LINKED ARTICLE: This article is commented on by Onat, pp. 1086–1087 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12050