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Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca²⁺ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca²⁺ channels has shown promise in preclinical studies, but clinical trials have been disappointing and combinatorial approaches are needed. We assessed efficacy of multiple combinations of three Ca²⁺ channel inhibitors at reducing secondary degeneration following partial optic nerve transection in rat. We used lomerizine to inhibit voltage gated Ca²⁺ channels; oxidised adenosine-triphosphate (oxATP) to inhibit purinergic P2X₇ receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca²⁺ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only the three Ca²⁺ channel inhibitors delivered in …