Involvement of N-methyl-D-aspartate receptors and nitric oxide in the anticonvulsant effects of dantrolene against pentylenetetrazole-induced seizures in mice

Abstract

ObjectiveN-methyl-d-aspartate (NMDA) receptors and nitric oxide (NO) have important roles in the pathology and treatment of pentylenetetrazole (PTZ)-induced seizures. We aimed to show the involvement of these two systems in the anticonvulsant effects of dantrolene against PTZ-induced seizures. MethodsThe male albino Swiss strain of mice (N=56) randomly allocated to the seven separate groups and treated with dantrolene (40mg/kg), dantrolene (40mg/kg)+L-arginine (100mg/kg, a NO donor), dantrolene (40mg/kg)+N-Nitroarginine methyl ester (L-NAME) (100mg/kg, a NO synthase inhibitor), dantrolene (40mg/kg)+NMDA (50mg/kg), dantrolene (40mg/kg)+MK801 (1mg/kg, a selective NMDA antagonist), Diazepam (5mg/kg, the positive control) and saline (the negative control). Seizures were induced by intraperitonial injection of PTZ (90mg/kg). The onsets of clonic and tonic-clonic seizures, as well as the death of animals, were recorded. ResultsDantrolene significantly increased the onset of clonic, tonic-clonic seizures and death of animals challenged with PTZ. The onset of tonic-clonic seizure in animals treated with dantrolene alone and dantrolene+L-NAME was higher than the control group. In contrast, the onset of tonic-clonic seizure in the animals treated with dantrolene+L-arginine was significantly lower than the dantrolene-treated group. The onset of clonic and tonic-clonic seizures in animals treated with dantrolene+MK801 were significantly higher than the control and dantrolene+NMDA groups. ConclusionDantrolene protected animals against PTZ-induced seizures and mortality. The inhibition of NO synthase and NMDA receptors may contribute to the dantrolene anticonvulsant effects on the PTZ-induced seizure.