Novel CGRP receptor antagonist, Rimegepant, could ameliorate CGRP-mediated apoptosis and ECM degradation in vitro. (a) Rimegepant concentration screening was carried out using CCK 8 assay, and the results showed that Rimegepant less than 10 μM is nontoxic to human NP cells. (b) Rimegepant could restore CGRP-mediated decreased cell viability in human NP cells. (c, d) TUNEL assay revealed that TUNEL-positive NP cells were increased significantly in the CGRP group, whereas human NP cells treated with CGRP plus Rimegepant showed decreased TUNEL-positive NP cells compared to the control group. (e, f) Immunofluorescence analysis suggested less protein translation of aggrecan and higher protein translation of MMP 3 in CGRP-treated human NP cells. However, Rimegepant could reverse these effects. ∗/#p < 0.05, ∗∗/##p < 0.01, ∗∗∗/###p < 0.001, and ∗∗∗∗/####p < 0.0001; ns: no significance. Scale bar = 100 μm.