Amelioration of Pentylenetetrazole-Induced Seizures by Modulators of Sigma, N-Methyl D Aspartate, and Ryanodine Receptors in Mice

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 anti-convulsant activity of opipramol.