The effect of acute aripiprazole treatment on chemically and electrically induced seizures in mice: The role of nitric oxide |
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| Institution: | 1. Department of Pharmacology and Toxicology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran;2. Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;3. Department of Pharmacology and Toxicology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran;4. Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;1. Polish Academy of Sciences, Institute of Biochemistry and Biophysics, Warsaw, Poland;2. School of Medicine, Cardiff University, Cardiff, United Kingdom;3. International Institute of Molecular and Cell Biology, Warsaw, Poland;4. Center for Integrated Protein Science at the Department Chemie, Lehrstuhl für Biochemie, Technische Universität München, Garching, Germany;5. Proteros biostructures GmbH, Martinsried, Germany;6. Schools of Chemistry and Biosciences, Cardiff University, Cardiff, United Kingdom;1. Graduate Program in Health Sciences, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil;2. Graduate Program in Pharmaceutical Sciences, Universidade Federal de Sergipe, São Cristóvão, Sergipe, Brazil;1. Division of Research and Development, Pharmin USA, LLC, SanJose, California, USA.;2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran |
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| Abstract: | Aripiprazole is an antipsychotic drug which acts through dopamine and serotonin receptors. Aripiprazole was noted to have antiseizure effects in a study on mice, while it induced seizures in a few human case reports. Dopaminergic and serotonergic systems relate to nitric oxide, and aripiprazole also has effects on dopamine and serotonin receptors. This study investigated the effects of aripiprazole on seizures and the potential role of nitric oxide in the process. The following three models were examined to explore the role of aripiprazole on seizures in mice: 1 — pentylenetetrazole administered intravenously, 2 — pentylenetetrazole administered intraperitoneally, and 3 — electroshock. Aripiprazole administration delayed clonic seizure in intravenous and intraperitoneal pentylenetetrazole models. In the electroshock-induced seizure model, tonic seizure and mortality protection percent were increased after aripiprazole administration. In intraperitoneal administration of pentylenetetrazole, aripiprazole effects on clonic seizure latency were significantly decreased when l-NAME — a nonselective nitric oxide synthase (NOS) inhibitor, 7-nitroindazole — a selective neuronal NOS (nNOS) inhibitor, or aminoguanidine — a selective inducible NOS (iNOS) inhibitor was injected before aripiprazole administration. In the intravenous pentylenetetrazole method, administration of l-NAME or aminoguanidine inhibited aripiprazole effects on clonic seizure threshold. Aminoguanidine or l-NAME administration decreased aripiprazole-induced protection against tonic seizures and death in the electroshock model. In both intravenous and intraperitoneal seizure models, aripiprazole and l-arginine coadministration delayed the onset of clonic seizures. Moreover, it increased protection against tonic seizures and death in intraperitoneal pentylenetetrazole and electroshock models. In conclusion, the release of nitric oxide via iNOS or nNOS may be involved in anticonvulsant properties of aripiprazole. |
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