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CC BY-NC-ND 4.0 · International Journal of Epilepsy 2017; 04(02): 112-118
DOI: 10.1016/j.ijep.2017.10.001
Research paper
Thieme Medical and Scientific Publishers Private Ltd.

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

Akbarzadeh Samad
a   Department of Biochemistry, Bushehr University of Medical Sciences, Bushehr, Iran
,
Heidary Fatemeh
b   School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
,
Keshavarz Mojtaba
c   Department of Pharmacology, Bushehr University of Medical Sciences, Bushehr, Iran
d   Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
› Author Affiliations
Further Information

Publication History

Received: 11 July 2017

Accepted: 09 October 2017

Publication Date:
06 May 2018 (online)

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Abstract

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.

Keywords

Dantrolene - Nitric oxide - N-methyl-D-Aspartate - Pentylenetetrazole - Seizure
 

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