Effect of 7-nitroindazole and NG-nitro-L-arginine on the protective action of clobazam in the maximal electroshock-induced seizures in mice
DOI:
https://doi.org/10.12923/Keywords:
7-Nitroindazole, NG-nitro-L-arginine, clobazam, nitric oxide, maximal electroshock seizure test.Abstract
The aim of this study was to determine effect 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 clobazam (CLB – a second-generation antiepileptic drug) in the maximal electroshock (MES)-induced seizure model in mice. Electroconvulsions were produced in adult male Albino Swiss mice by means of an alternating current (50Hz, 500V, 25mA, ear-clip electrodes, 0.2s stimulus duration). The anticonvulsant action of CLB in the MES test was expressed as median effective doses (ED50 values) of the drug, protecting 50% of animals tested against MES-induced seizures. The acute adverse-effect potentials of CLB in combination with 7NI and NNA were evaluated in the chimney test (motor coordination), passive avoidance task (long-term 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 CLB by reducing its ED50 value from 15.14 mg/kg to 10.23 mg/kg (p<0.05). Similarly, 7NI at the lower dose of 25 mg/kg also potentiated the anticonvulsant action of CLB, although the results did not attain statistical significance. In contrast, NNA (40 mg/kg; i.p.) had no impact on the anticonvulsant effect of CLB. Moreover, none of the examined combinations of CLB with 7NI and NNA affected motor coordination, long-term memory, and skeletal muscular strength in mice. Based on this preclinical study, one can conclude that 7NI significantly enhanced, whereas NNA had no effect on the anticonvulsant activity of CLB against MES-induced seizures in mice.
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