Noxious pain signals are transduced in the peripheral nervous system as action potentials, which are greatly defined by the activities of the voltage-gated sodium channels (NaVs), blocking NaVs is thus a valuable strategy for pain treatment. Herein we reported the characterization and mechanistical study of a novel NaVs antagonist, 2-(2-(diethylamino)ethyl)indeno[1,2,3-de]phthalazin-3(2H)-one(named as C65780). This compound potently inhibited the pain targets of NaV1.7, NaV1.8 and NaV1.9 channel at -100 mV holding with an IC50 of 11.3 ± 0.4 μM , 2.7 ± 0.3 μM and 19.2 ±2.3 μM, repectively. Analyzing the effect of C65780 on gating kinetics of the NaV1.7 and NaV1.8 channels revealed it preferably facilitated channels’ slow inactivation, by greatly shifting channels’ inactivation-voltage relationships to the hyperpolarized direction, increasing the plateau proportion of inactivated channels, and accelerating channels’ inactivation development whereas hindering their time-dependent recovery from it. Meanwhile, C65780 use-dependently inhibited NaV1.7, as illustrated by enhanced currents inhibition at high stimuli frequency and at more depolarized holding potential. Moreover, C65780 exhibited a comparable analgesic effect as the neuropathic pain drug amitriptyline in various pain animal models when orally administrated, possibly by inhibiting the DRG NaVs. An expanded survey of C65780’ activity on other NaVs revealed its inhibitory effect on NaV1.2-1.5 channels like amitriptyline, but it did not caused obvious toxic effect and locomotion inhibition in a forced-swimming test in mice at the pain-relieving doses. Collectively, we concluded that C65780 trapped NaVs in the slow-inactivated state and might be a valuable drug candidate for pain treatment.