Influence of 7-nitroindazole and NG-nitro-L-arginine on the anticonvulsant activity of loreclezole in maximal electroshock-induced seizures in mice

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