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Title

AMELIORATION OF PENTYLENETETRAZOLE-INDUCED SEIZURES BY MODULATORS OF SIGMA, N-METHYL-DASPARTATE, AND RYANODINE RECEPTORS IN MICE

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 Start Page 195 | End Page 201

Abstract

 Background: SIGMA receptors, N-methyl-D-aspartate (NMDA) antagonist, and modulators of intracellular calcium may be useful for seizure control. Therefore, we aimed to evaluate the antiepileptic effects of OPIPRAMOL, a SIGMA receptor agonist, against PENTYLENETETRAZOLE (PTZ) -induced seizures in mice and assess KETAMINE and CAFFEINE interaction with the antiepileptic effects of OPIPRAMOL.Methods: PTZ (100 mg/kg) was used for the induction of seizure in 72 male albino Swiss strain of mice (n=8).OPIPRAMOLe (10, 20, and 50 mg/kg), KETAMINE (50 mg/kg), CAFFEINE (200 mg/kg), OPIPRAMOLe (20 mg/kg) plus KETAMINE (50 mg/kg), OPIPRAMOLe (20 mg/kg) plus CAFFEINE (200 mg/kg), diazepam (5 mg/kg as a positive control), and the vehicle were administered interaperitoneally 30 minutes before the injection of PTZ. The latency was recorded for the clonic, tonic-clonic seizures, and death of animals after the injection of PTZ. Kruskal-Wallis test followed by Dunn’s test was used for the analysis of data. Statistical analysis was performed with the SPSS software version 23.0 and P<0.05 was considered as the significant level.Results: OPIPRAMOL (20 mg/kg) increased the latency for the PTZ-induced clonic (44%, P=0.021) and tonic-clonic (130.80%, P=0.043) seizures compared with the vehicle-treated group.Animals treated with OPIPRAMOL (20 mg/kg) plus CAFFEINE (200 mg/kg) had a significantly higher onset of PTZ-induced clonic and tonic-clonic seizures compared with the control (P=0.046 and<0.001, respectively). KETAMINE combined with OPIPRAMOL increased the onset of tonic-clonic seizure compared with the vehicle-treated groups (P<0.001).Conclusion: OPIPRAMOL attenuated the seizures induced by the PTZ. KETAMINE and CAFFEINE had no effect on the anticonvulsant activity of OPIPRAMOL.

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