In vitro Evaluation of Memantine and Nicotinamide Combination for Synergistic Cytotoxicity in U87MG Glioblastoma Cells

INTRODUCTION: Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant brain tumors. Conventional therapies often fail to produce durable clinical responses due to rapid progression and therapeutic resistance. Drug repurposing offers a promising strategy to identify effective combinations using existing drugs. METHODS: This study evaluated the synergistic effects of Memantine (MEM), an NMDA receptor antagonist, and Nicotinamide (NAM), a form of vitamin B3, in U87MG GBM cells. The Chou- Talalay fixed-ratio (1:1) design was employed across five concentration levels. Cytotoxicity and anti-migratory effects were assessed after 24 h of treatment, and data were analyzed using CompuSyn (v2.0). RESULTS: The MEM-NAM combination exhibited significant synergistic cytotoxicity with a combination index (CI) of 0.45 ± 0.08. The IC₅₀ values were 48.2 ± 2.6 μM for Memantine and 1297.90 ± 2.46 μM for Nicotinamide. The combination also markedly inhibited GBM cell migration compared with single-drug treatments. DISCUSSION: The synergistic interaction between MEM and NAM suggests a complementary mechanism that enhances anti-proliferative and anti-migratory responses in GBM cells. This supports the therapeutic potential of repurposed drug combinations in overcoming tumor resistance. CONCLUSION: The Memantine-Nicotinamide combination demonstrates significant in vitro synergy and anti-migratory effects against glioblastoma cells, warranting further investigation in preclinical and clinical models to validate its translational potential.