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

Objective N-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. Methods The male albino Swiss strain of mice (N = 56) randomly allocated to the seven separate groups and treated with dantrolene (40 mg/kg), dantrolene (40 mg/kg) + L-arginine (100 mg/kg, a NO donor), dantrolene (40 mg/kg) + N-Nitroarginine methyl ester (L-NAME) (100 mg/kg, a NO synthase inhibitor), dantrolene (40 mg/kg) + NMDA (50 mg/kg), dantrolene (40 mg/kg) + MK801 (1 mg/kg, a selective NMDA antagonist), Diazepam (5 mg/kg, the positive control) and saline (the negative control). Seizures were induced by intraperitonial injection of PTZ (90 mg/kg). The onsets of clonic and tonic-clonic seizures, as well as the death of animals, were recorded. Results Dantrolene 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. Conclusion Dantrolene 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