Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine

Payandemehr, Borna; Rahimian, Reza; Bahremand, Arash; Ebrahimi, Ali; Saadat, Seyedehpariya; Moghaddas, Peiman; Fadakar, Kaveh; Derakhshanian, Hoda; Dehpour, Ahmad Reza

doi:10.1016/j.physbeh.2013.05.022

Cited by 27 publications

(14 citation statements)

References 59 publications

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“…Our data showed that non-effective doses of aminoguanidine as a preferential iNOS inhibitor and 1400W as a highly specific iNOS inhibitor increased the anticonvulsant properties of licofelone in the intravenous PTZ model of seizure. However, there are some studies which have reported non-effect or even protective effects for iNOS activation in seizure susceptibility [25,29,59]. In contrast to our data, some investigators showed iNOS inhibition (by aminoguanidine) reversed the anticonvulsant effects of acute or chronic atorvastatine treatment in different seizure paradigms [59,60].…”

Section: Discussioncontrasting

confidence: 99%

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A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice

et al. 2015

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Licofelone is a COX/5-LOX inhibitor, which recently was approved as an effective treatment for osteoarthritis. Beside its analgesic and anti-inflammatory effects, some reports show neuro-protective properties for this agent in central nervous system. Several lines of evidence declare the involvement of COX or LOX isoenzymes in epileptic disorders. To set the foundation for future research into the neurobiology of licofelone as a potential therapeutic agent, we studied the effect of licofelone in an animal model of epilepsy. Although different neurotransmitters and neuro-modulators like nitric oxide were introduced as suggested targets of licofelone, the underlying mechanisms of central effects of this drug are not still fully understood. We have utilized pentylenetetrazole-induced clonic seizure model to investigate the behavioral consequences of licofelone administration and its possible mechanisms in seizure susceptibility. Licofelone revealed anticonvulsant properties at the dose of 10 mg/kg (i.p) or higher in mice. Pre-treatment with NO (nitric oxide) donor, L-arginine, reversed this anticonvulsant effects dose dependently. L-NAME, as a non-selective nitric oxide synthase (NOS) inhibitor, potentiated the anticonvulsant effects of licofelone. A neuronal NOS inhibitor, 7-NI did not affect seizure threshold alone or in combination with licofelone. Using non-effective doses of selective inhibitors of inducible NOS, aminoguanidine or 1400W, significantly increased the seizure threshold when were accompanied by licofelone in low doses. These data support the involvement of NO as an important role player in the central neuro-protective properties of licofelone. Furthermore, it implies that down regulation of iNOS seems crucial for anticonvulsant properties of this COX/5-LOX inhibitor in seizure susceptibility.

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Section: Discussioncontrasting

confidence: 99%

“…Various studies propose that both neuronal and inducible isoforms of NOS participate in several crucial brain processes [21,22]. Studies have been shown that NO have proconvulsant or anticonvulsant effects, depending on the seizure models, source of NO and other neurotransmitter systems modulation [23][24][25].…”

Section: Introductionmentioning

confidence: 99%

A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice

et al. 2015

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“…Aripiprazole was injected 60 min before PTZ or electroshock (ECT). The doses of drugs were chosen based on previously published studies and pilot experiments [18,19,20,21]. All injections and tests were conducted between 9:00 a.m. and 3:00 p.m. …”

Section: Methodsmentioning

confidence: 99%

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

et al. 2015

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Almost all antipsychotics have been associated with a risk of epileptic seizure provocation. Aripiprazole is a novel atypical antipsychotic. The risk of seizures with aripiprazole is reported to be the lowest among atypical agents. In this study, we investigated the effect of aripiprazole on seizure of mice in sub-chronic treatments. We also examined the interaction of nitric oxide (NO) with aripiprazole in seizure experiments. Mice received aripiprazole for 6 days and then on the 7th day aripiprazole was injected 60 min before intraperitoneal pentylenetetrazole or electroshock. L-NAME (non-selective NO synthase (NOS) inhibitor), 7-nitroindazole (neuronal NOS selective inhibitor), aminoguanidine (inducible NOS selective inhibitors) or L-arginine (NO donor), all were injected 5 min before aripiprazole in separate groups. The results of both seizure models demonstrated anti-epileptic properties of aripiprazole in sub-chronic administrations. Co-administration of aripiprazole and selective and non-selective NOS inhibitors prevented the anticonvulsant effect of aripiprazole. While L-arginine and aripiprazole co-administration increased the clonic seizure threshold and protection against tonic seizure and death, these effects were not significant. The current results indicated that aripiprazole has anticonvulsant effects probably through the release of NO.

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“…8,12,13 Endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) are three nitric oxide synthase isoforms. 14,15 All the three isoforms are expressed in the brain throughout aging and pathologic conditions. 10,15,16 Among these isoenzymes, iNOS plays roles in various inflammatory and patho-physiological processes 8 and also in oxidative/nitrosative induced cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Aminoguanidine against Sodium Metavanadate-Induced Spatial Memory Retention Impairment in Morris Water Maze

et al. 2019

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Background: Vanadium is a potential neurotoxic agent widely distributed in the environment. Understanding the neurotoxic mechanisms of vanadium on learning and memory seems necessary. Methods: We investigated the time-dependent (1-week, 2- week and 4-week) effects of sodium metavanadate (SMV) (25 mg/kg/day; pre-training oral administration) and 4-day intraperitoneal injections of aminoguanidine (AG) as a selective inducible nitric oxide synthase inhibitor (10, 50, and 100 mg/kg) on spatial memory retention in Morris water maze. Animals were trained for 4 days and tested 48 h after the last training trial. Results: The data showed that 4-week oral pre-treatment with SMV (25 mg/kg/day) induced spatial memory retention deficits and decreased the time spent in the target quadrant. We found that 4-day administration of different doses of AG during training trials significantly decreased the time and distance of finding the hidden platforms. Additionally, SMV-induced spatial memory retention impairments were prevented in animals received combined SMV (25 mg/kg/day, 4 weeks) and AG (10 mg/kg/day, 4 days). Conclusion: Our findings showed the protective role of AG on SMV-induced spatial memory retention deficits.

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Role of nitric oxide in additive anticonvulsant effects of agmatine and morphine

Cited by 27 publications

References 59 publications

A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice

A COX/5-LOX Inhibitor Licofelone Revealed Anticonvulsant Properties Through iNOS Diminution in Mice

The Effects of Sub-Chronic Treatment with Aripiprazole on Pentylenetetrazole- and Electroshock-Induced Seizures in Mice: The Role of Nitric Oxide

Protective Effects of Aminoguanidine against Sodium Metavanadate-Induced Spatial Memory Retention Impairment in Morris Water Maze

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