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Neuroprotective Effect of Sumatriptan in Pentylenetetrazole-Induced Seizure Is Mediated Through N-Methyl-D-Aspartate/Nitric Oxide and Camp Response Element-Binding Protein Signaling Pathway Publisher Pubmed



Mumtaz F1, 2, 3 ; Rashki A1, 4 ; Imran Khan M5 ; Shadboorestan A6 ; Abdollahi A7 ; Ghazikhansari M2 ; Alotaibi G8 ; Dehpour AR1, 2
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. International Campus of Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmacology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
  5. 5. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
  6. 6. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  7. 7. Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran
  8. 8. Department of Pharmaceutical Sciences, College of Pharmacy, Al-Dawadmi Campus, Shaqra University, Shaqra, Saudi Arabia

Source: Fundamental and Clinical Pharmacology Published:2022


Abstract

Seizure occurs as a result of uncontrolled electrical disturbances within the brain. Various biomolecules such as N-methyl-D-aspartate (NMDA), nitric oxide (NO), and cAMP response element-binding protein (CREB) have been implicated in the pathophysiology of seizure. Sumatriptan is a specific 5-Hydroxytryptamine 1B/1D receptor agonist and has neuroprotective effects in various neuropsychiatric disorders. In the current study, we tried to investigate the possible interaction of sumatriptan with NMDA/NO and CREB signaling pathway in PTZ induced seizure. For this purpose, various agonist and antagonist of NMDA such as MK-801 and Ketamine, NO precursor L-ARG, and NOS inhibitors L-NAME and 7-NI were co-administered with sumatriptan in PTZ induced seizure model. The level of nitrite in mice hippocampus was determined by Griess reaction. The gene expression of NR1, NR2A, NR2B, and CREB were quantified by quantitative real time-polymerase chain reaction (qRT-PCR). Furthermore, the involved neuronal nitric oxide synthase (nNOS) protein expression was examined via western blot analysis. Effective dose of sumatriptan (1.2 mg/kg) alone and subeffective dose of sumatriptan (0.3 mg/kg) in combination with NMDA and/or NO antagonist showed significant (P < 0.001) anticonvulsant activity in mice. Furthermore, sumatriptan significantly inhibited the PTZ-induced mRNA expression of NR2A (P < 0.0001), NR2B (P < 0.05), and CREB (P < 0.01). Also, the expression of nNOS protein in PTZ treated group was reversed by sumatriptan (P < 0.01). Hence, current findings suggest that the anticonvulsant effect of sumatriptan was due to down regulation of NMDA/NO and CREB signaling pathway. © 2021 Societe Francaise de Pharmacologie et de Therapeutique
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