The aim of the study was to determine the effects of 7-nitroindazole (7NI - a preferential neuronal nitric oxide synthase [NOS] inhibitor) and NG-nitro-L-arginine (NNA – a non-selective NOS inhibitor) on the anticonvulsant action of loreclezole (LCZ – an innovative antiepileptic drug) in maximal electroshock-induced seizures (MES) in mice. Electroconvulsions were produced in mice by means of an alternating current (50 Hz, 500 V, 25 mA, administered by ear-clip electrodes, 0.2-s stimulus duration, tonic hind limb extension taken as the end point). The anticonvulsant action of LCZ in the MES test was expressed as the median effective dose (ED50 value) of the drug, protecting 50% of animals tested against MES-induced seizures. The acute adverse-effect potentials of LCZ in combination with 7NI and NNA were evaluated in the chimney test (motor coordination), step-through passive avoidance task (longterm memory), and grip-strength test (skeletal muscular strength) in mice. Results indicate that 7NI (50 mg/kg; i.p.) significantly enhanced the anticonvulsant action of LCZ by reducing its ED50 value from 108.9 mg/kg to 60.5 mg/kg (P<0.05). Similarly, 7NI at the lower dose of 25 mg/kg also enhanced the antiseizure action of LCZ by lowering the ED50 value of LCZ from 108.9 mg/kg to 82.7 mg/kg, although the results did not attain statistical significance. In contrast, NNA (40 mg/kg; i.p.) attenuated the anticonvulsant effects of LCZ by increasing its ED50 value from 108.9 mg/kg to 137.4 mg/kg; however, statistical analysis of the data revealed no significance between both ED50 values. Moreover, none of the examined combinations of LCZ with 7NI and NNA affected motor coordination, long-term memory, or skeletal muscular strength in the mice. Based on this preclinical study, one may conclude that 7NI significantly enhanced, whereas NNA attenuated the antiseizure affects of LCZ against MES-induced seizures in mice.