In in vitro mouse hippocampal slices we investigated whether cyclocreatine is capable of entering brain cells independently of the creatine transporter and if it reproduces the neuroprotective effect of creatine. Our study shows that cyclocreatine does not increase the creatine content, but is taken up as such and then phosphorylated to phosphocyclocreatine. This uptake is largely blocked by inactivation of the creatine transporter, however some cyclocreatine is taken up and posphorylated even after such inactivation. Thus, cyclocreatine sets up a cyclocreatine/phosphocyclocreatine system in the brain independently of the creatine transporter. Cyclocreatine did not delay the disappearance of the evoked synaptic potentials during anoxia in hippocampal slices, unlike creatine which exerts a neuroprotective effect.