Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway

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Mahernia Shabnam; SHARIFI NIUSHA; Hassanzadeh Malihe; RAHIMI NASTARAN; Pourshadi Nastaran; AMANLOU ARASH; DEHPOUR AHMAD REZA; AMANLOU MASSOUD

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Journal: PHARMACEUTICAL SCIENCES Year:2018 | Volume:24 | Issue:4 Page(s): 250-256

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Title

Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway

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Keywords

Barbituric acid

Nitric oxide

Nitric oxide synthase inhibitors

Pentylenetetrazole

Seizure

Mice

Abstract

Background: Barbituric acid derivatives have long been used as central nervous system (CNS) suppressants, such as sedatives, hypnotics and anticonvulsants. In addition, previous studies have implicated the involvement of Nitric oxide (NO) in the anticonvulsive effects of barbiturates in CNS. Therefore, the purpose of this study was to figure out the effects of a novel class of Barbituric acid derivatives on Pentylenetetrazole (PTZ)-induced Seizures in male Mice. Methods: Thirteen synthesized Barbituric acid derivatives (a-m) and phenobarbital were administered intraperitoneally (i. p. ) 30 min before induction of Seizures by PTZ administration. The mechanisms of PTZ-induced Seizures in the Mice was evaluated using a non-selective Nitric oxide synthase (NOS) inhibitor, selective inducible NOS (iNOS) inhibitor, a selective neuronal NOS (nNOS) inhibitor, and NO substrate. Results: Administration of most of the above mentioned derivatives significantly increased the Seizures threshold (P<0. 001). The most potent derivative (compound a), was chosen in order to investigate the mechanism of action involving in anticonvulsant activity. Administration of a non-selective NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and a selective nNOS inhibitor, 7-nitroindazole (7-NI) reversed anticonvulsant activity of compound a. However, injection of the Nitric oxide precursor, L-arginine (L-Arg) and a selective iNOS inhibitor, aminoguanidine (AG), did not change anticonvulsant activity of the mentioned compound. Conclusion: These results indicated that the NO system, specifically nNOS may contribute to the anticonvulsant activity of benzylidene Barbituric acid derivative a. Therefore, this compound is a good candidate in order to designing new anticonvulsant medications.

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APA: Copy

Mahernia, Shabnam, SHARIFI, NIUSHA, Hassanzadeh, Malihe, RAHIMI, NASTARAN, Pourshadi, Nastaran, AMANLOU, ARASH, DEHPOUR, AHMAD REZA, & AMANLOU, MASSOUD. (2018). Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway. PHARMACEUTICAL SCIENCES, 24(4), 250-256. SID. https://sid.ir/paper/740942/en

Vancouver: Copy

Mahernia Shabnam, SHARIFI NIUSHA, Hassanzadeh Malihe, RAHIMI NASTARAN, Pourshadi Nastaran, AMANLOU ARASH, DEHPOUR AHMAD REZA, AMANLOU MASSOUD. Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway. PHARMACEUTICAL SCIENCES[Internet]. 2018;24(4):250-256. Available from: https://sid.ir/paper/740942/en

IEEE: Copy

Shabnam Mahernia, NIUSHA SHARIFI, Malihe Hassanzadeh, NASTARAN RAHIMI, Nastaran Pourshadi, ARASH AMANLOU, AHMAD REZA DEHPOUR, and MASSOUD AMANLOU, “Benzylidene Barbituric Acid Derivatives Shown Anticonvulsant Activity on Pentylenetetrazole-Induced Seizures in Mice: Involvement of Nitric Oxide Pathway,” PHARMACEUTICAL SCIENCES, vol. 24, no. 4, pp. 250–256, 2018, [Online]. Available: https://sid.ir/paper/740942/en

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