Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors

Mohseni, Gholamreza; Ostadhadi, Sattar; Akbarian, Reyhaneh; Chamanara, Mohsen; Javidan, Abbas Norouzi; Dehpour, Ahmad Reza

doi:10.1016/j.yebeh.2016.08.001

Cited by 16 publications

(5 citation statements)

References 71 publications

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“…The results confer anticonvulsant properties on endothelial NO but proconvulsant on neuronal NOS. This attribution of convulsant properties to neuronal NO is in agreement with the finding that the anticonvulsant effect of dextrometrophan is mediated by a decline in nNOS activity (28). Proconvulsant or anticonvulsant properties of NO may be explained by the opposite effects of endothelial and neuronal NO on GABA-T activity, and hence on GABA levels.…”

Section: Discussionsupporting

confidence: 90%

“…Correlation between brain gamma amino butyric acid transaminase (GABA-T) activity and brain GABA levels under the influence of l-arginine (l-Arg), Nω-nitro-l-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). that NMDA receptors/NO pathway contribute to the anticonvulsant effect of different drugs such as D-penicillamine (11), dextrometrophan (28) and lithium (29).…”

Section: Resultsmentioning

confidence: 99%

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Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

2018

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In an attempt to clarify the controversial role of nitric oxide (NO) in seizures, the effects of NO on brain GABA transaminase (GABA-T) activity and GABA levels were investigated. To this aim, the effects of the substrate (l-arginine) and inhibitors (Nω-nitro-l-arginine methyl ester, 7-nitroindazole) of NO synthase (NOS) on GABA-T activity and GABA levels in vitro and ex vivo were analyzed. In vitro NO diminished GABA-T activity and increased GABA. Ex vivo NO modified GABA-T activity and GABA levels biphasically. Inhibition of endothelial and neuronal NOS (eNOS and nNOS) had opposite effects on GABA-T activity and GABA levels, even during seizures induced by pentylenetetrazole. Different effects of NO on GABA-T activity and on GABA levels, depending on the NOS isoform involved, may explain its contradictory role in seizures, the endothelial NOS acting as an anticonvulsant and the neuronal NOS as a proconvulsant. nNOS inhibitors may represent a new generation of antiepileptics.

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Section: Discussionsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

2018

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“…NO plays essential roles in the central nervous system as a neuronal messenger. It is also a modulator that mainly participates in several neural processes and diseases, such as antinociception, tolerance, as well as seizures with both anti‐ and proconvulsive characteristics in different models like kindling and electroshock . It has been implied that NO is involved in bimodal effects of morphine and modafinil on PTZ‐induced clonic seizures in mice.…”

Section: Introductionmentioning

confidence: 99%

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Roodsari

Bahramnejad

Rahimi

et al. 2019

Annals of the New York Academy of Sciences

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Methadone is a synthetic opioid used to treat opiate withdrawal and addiction. Studies have demonstrated the impact of methadone on seizure susceptibility. This study investigated the modulatory impacts of acute and subchronic (three times daily for 5 days) intraperitoneal methadone treatment on pentylenetetrazole‐induced clonic seizure threshold (CST) in mice, as well as the involvement of the nitric oxide, N‐methyl‐d‐aspartate (NMDA), and µ‐opioid pathways. Acute administration of different doses of methadone (0.1, 0.3, 1, and 3 mg/kg) 45 min before CST significantly decreased the seizure threshold. Additionally, pretreatment with noneffective doses of an opioid receptor antagonist (naltrexone) and NMDA receptor antagonists (ketamine and MK‐801) inhibited methadone's proconvulsive activity in the acute phase, while l‐NAME (a nonspecific nitric oxide synthase (NOS) inhibitor) did not affect that activity. In the subchronic phase, methadone (3 mg/kg) demonstrated an anticonvulsive effect. Although subchronic pretreatment with noneffective doses of l‐NAME and 7‐nitroindazole (a specific neuronal NOS inhibitor) reversed methadone's anticonvulsive activity, aminoguanidine (a specific inducible NOS inhibitor), naltrexone, MK‐801, and ketamine did not change methadone's anticonvulsive characteristic. Our results suggest that NMDA and µ‐opioid receptors may be involved in methadone's proconvulsive activity in the acute phase, while methadone's anticonvulsive activity may be modulated by neuronal NOS in the subchronic phase.

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“…The fact that the level of nitrate in the adult rats went up after seizures and SE caused by pilocarpine suggested that the level of ROS may have gone up, which could be part of how seizures damage neurons. Nitric oxide level controls some important biological signals in several bodily processes, such as neurotransmission, blood pressure regulation, body defence mechanisms, smooth muscle relaxation, and immune regulation 15 . It was found that seizures caused by pilocarpine cause the breakdown of nitric oxide to speed up.…”

Section: Discussionmentioning

confidence: 99%

Alleviating Potential of <i>Zingiber officinale</i> and Cow Urine Distillate Co-administered with Levetiracetam in Epileptic Rats: A Pharmacokinetic and Pharmacodynamics Approach

Solanki

Patel

et al. 2023

JNR

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Background: Epilepsy is a severe neurological condition that affects all ages of people. Complex pathways involved in pathogenesis make it complicated to treat; selected antiepileptic drug options are available for Epilepsy. There is a need for an hour to develop novel treatment approaches for epilepsy with lesser side effects. This research aimed to evaluate the alleviating role of bio-enhancers co-administered with levetiracetam for pilocarpine-induced epilepsy. Methodology: Pilocarpine (250 mg/kg) was used to develop epilepsy in rats. Levetiracetam (LEV) (140 mg/kg) was administered with Zingiber officinale Extract (ZOE) (15 mg/kg and 30 mg/kg) and Cow Urine Distillate (CUD) (1.5 ml/kg and 3 ml/kg). HPLC was used to evaluate drug concentration in blood. Serum nitrate, catalase, CRP, calcium level and calcium level of the brain, behavioural markers in rats were assessed and compared with the Leviteracetam group only. Result and Discussion: The present study showed that combining ZOE and CUD with levetiracetam was advantageous through substantial reduction (p < 0.05) in serum nitrate, CRP and increased catalase (p < 0.05), while reduced serum calcium compared to LEV alone. Combination of ZOE and CUD with levetiracetam treatment also reduced seizure behaviour and duration in rats. The bioavailability of LEV in plasma and brain was increased when epileptic rats were treated with LEV plus ZOE and CUD compared to disease control. Conclusion: Utilization of Zingiber officinale and CUD in combination with LEV was proven therapeutically effective in the epileptic model and used to lower the dose of LEV along with reducing seizure behaviour and time with the potential for the treatment of epilepsy.

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Anticonvulsant effect of dextrometrophan on pentylenetetrazole-induced seizures in mice: Involvement of nitric oxide and N-methyl-d-aspartate receptors

Cited by 16 publications

References 71 publications

Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels

Methadone's effects on pentylenetetrazole‐induced seizure threshold in mice: NMDA/opioid receptors and nitric oxide signaling

Alleviating Potential of <i>Zingiber officinale</i> and Cow Urine Distillate Co-administered with Levetiracetam in Epileptic Rats: A Pharmacokinetic and Pharmacodynamics Approach

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