In the present study, we used the L-type calcium channel blocker nimodipine, the endoplasmic reticulum (ER) calcium release blocker dantrolene and the calcium transport blocker in mitochondria ruthenium red (RuR), in NMDA induced neurotoxicity, to observe the most suitable combination for neuroprotection in cerebellar granular cell culture of rat pups. In addition we tested the effect of RuR on intact neuronal cells without adding NMDA into the flask, in order to compare the effects. As was expected, NMDA induced neuronal cell death. In NMDA induced neurotoxicity, RuR was the most neuroprotective agent of all three compounds tested, but interestingly, RuR alone was found to be neurotoxic in non-NMDA treated cultures. RuR showed neuroprotectivity in a dose dependent manner in NMDA toxicity. Dantrolene and nimodipine were also found to have neuroprotective properties in NMDA induced cell death in rat cerebellum. On the other hand, the combined application of the compounds was not found as protective as ruthenium red applications alone. The present study revealed a neurotoxic feature of ruthenium red, however we also demonstrated a neuroprotective role for it in NMDA-mediated neuron culture. This could be interpreted as a result of the partial agonistic effect of ruthenium red.