Levetiracetam opposes the action of GABAA antagonists in hypothalamic neurones

Poulain, Pierre; Mǎrgineanu, D.

doi:10.1016/s0028-3908(01)00185-x

Cited by 57 publications

(34 citation statements)

References 18 publications

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“…In addition to LEV, the other two ligands that can bind to SV2A are: brivaracetam (BRV) and seletracetam (SLE). The possible mechanisms are described below in Tables 3 [35][36][37][38][39][40][41][42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

“…LEV can reduce AMPA-induced current as well as variation and frequency of low excitatory postsynaptic current [41,42]. SLE has no effect on inhibitory and excitatory neurotransmitters [46].…”

Section: Discussionmentioning

confidence: 99%

“…It was reported that LEV could inhibit N type calcium channel regulating calcium influx, and further inhibit Ca2+ overloadinduced apoptosis [35][36][37]. Green et al discovered that LEV may affect GABA release after cerebral ischemia [40,41] or affect GABA antagonist activity [42] and may further reduce the neuronal damage induced by enhanced effects of excitatory amino acids. Another study found that one of the main metabolic products of LEV is a histone deacetylase inhibitor, which is also mainly involved in apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Not reported Repress voltage dependent Na channel [35] Not reported No direct effect, indirectly enhance GABA pathways [40] SLE Repress high voltage-activated N type, part Q type channel [41] No effect [42] Not reported No direct effect [43] little side effects and well tolerance and has been widely used as an antiepileptic drug, LEV is becoming a very promising neuron-protective medicine for patients who suffer from neuronal injury induced by acute cerebral I/P.…”

Section: Brvmentioning

confidence: 99%

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Levetiracetam Prevents Perforin Mediated Neuronal Injury Induced by Acute Cerebral Ischemia Reperfusion

Zhang

Zuo

et al. 2015

Mol Neurobiol

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The purpose of this study is to explore the neuroprotection mechanism of levetiracetam (LEV) with acute focal cerebral ischemia-reperfusion (I/P) mouse. The cerebral artery I/P animal model was prepared with a middle artery cerebral occlusion method. For drug intervention, mice were intraperitoneally injected with LEV with a dose of either 15 or 150 mg/kg. Neuronal injury was evaluated by measuring the infarct area, apoptosis ratio, and observation of blood-brain barrier ultrastructure with transmission electron microscope. CD8(+) antibody and perforin antibody were used to make cross-reference screen through flow cytometry to determine a perforin-positive rate in CD8(+) T lymphocytes (PFN + %). Injection of LEV can reduce infarct area, apoptosis ratio, and blood-brain barrier damage 24 h later after acute I/P in WT mice. In vitro, perforin can lower hippocampal neuron viability. In vivo, removing perforin can relieve neuronal injury. High dose injection of LEV (150 mg/kg) can inhibit perforin secreting from CD8(+)T lymphocytes. In addition, LEV can still protect neurons with perforin knockout mice. Therefore, our results suggested that LEV may contribute to neuron protection after cerebral ischemia reperfusion. The possible mechanism may be related with perforin release. However, we cannot roll out other mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Brvmentioning

confidence: 99%

See 2 more Smart Citations

Levetiracetam Prevents Perforin Mediated Neuronal Injury Induced by Acute Cerebral Ischemia Reperfusion

Zhang

Zuo

et al. 2015

Mol Neurobiol

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“…Although its mechanism of action remains to be further characterized, it seems unrelated to any modulation of neuronal voltage-gated Na + or low-voltage-activated Ca 2+ (Ttype) channels (Zona et al, 2001). However, experimental evidence, both in vitro and in vivo, suggests a role of both calcium channels N-type (Lukyanetz et al, 2002) and GABAergic activity in LEV effects (Poulain and Margineanu, 2002;Rigo et al, 2002). Other investigations show that LEV delays rectifier K + currents in hippocampal neurons (Madeja et al, 2003) and also it is able to bind to SV2A protein, a synaptic vesicle protein that is an essential protein implicated in the control of exocytosis (Lynch et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Effects of Levetiracetam in Lipid Peroxidation Level, Nitrite–Nitrate Formation and Antioxidant Enzymatic Activity in Mice Brain After Pilocarpine-Induced Seizures

et al. 2007

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: Oxidative stress has been implicated in a large number of human degenerative diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent with broad-spectrum effects on seizures and animal models of epilepsy. Recently, it was demonstrated that the mechanism of LEV differs from that of conventional antiepileptic drugs. Objectifying to investigate if LEV mechanism of action involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate formation, catalase activity, and glutathione (GSH) content were measured in adult mice brain. The neurochemical analyses were carried out in hippocampus of animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg, s.c. (P400) produced a significant increase of lipid peroxidation level in hippocampus. LEV pretreatment was able to counteract this increase, preserving the lipid peroxidation level in normal value. P400 administration also produced increase in the nitrite-nitrate formation and catalase activity in hippocampus, beyond a decrease in GSH levels. LEV administration before P400 prevented the P400-induced alteration in nitrite-nitrate levels and preserved normal values of catalase activity in hippocampus. Moreover, LEV administration prevented the P400-induced loss of GSH in this cerebral area. The present data suggest that the protective effects of LEV against pilocarpine-induced seizures can be mediated, at least in part, by reduction of lipid peroxidation and hippocampal oxidative stress.

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