Levetiracetam inhibits the high-voltage-activated Ca2+ current in pyramidal neurones of rat hippocampal slices

Niespodziany, Isabelle; Klitgaard, Henrik; Margineanu, Doru Georg

doi:10.1016/s0304-3940(01)01884-5

Cited by 196 publications

(117 citation statements)

References 16 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…In general, such effects were measured in response to shortterm LEV application and were reported to produce small irreversible reductions in Ca 2ϩ current (Lukyanetz et al, 2002;Pisani et al, 2004;Costa et al, 2006;Martella et al, 2008); our data, which showed no short-term LEV effects, are in disagreement with those studies. However, Niespodziany et al (2001) investigated the time dependence of LEV effects on Ca V channels, and their finding that LEV required Ն30 min of perfusion to cause significant inhibition correlates well with our data. In the present study, LEV required prolonged external exposure to affect both Ca V channels and cholinergic transmission.…”

Section: Tablesupporting

confidence: 86%

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway

Vogl¹,

Mochida²,

Wolff³

et al. 2012

Mol Pharmacol

109

View full text Add to dashboard Cite

Levetiracetam (LEV) is a prominent antiepileptic drug that binds to neuronal synaptic vesicle glycoprotein 2A protein and has reported effects on ion channels, but with a poorly defined mechanism of action. We investigated inhibition of voltagedependent Ca 2ϩ (Ca V ) channels as a potential mechanism through which LEV exerts effects on neuronal activity. We used electrophysiological methods to investigate the effects of LEV on cholinergic synaptic transmission and Ca V channel activity in superior cervical ganglion neurons (SCGNs). In parallel, we investigated the effects of the inactive LEV R-enantiomer, (R)-␣-ethyl-2-oxo-1-pyrrolidine acetamide (UCB L060). LEV but not UCB L060 (each at 100 M) inhibited synaptic transmission between SCGNs in long-term culture in a time-dependent manner, significantly reducing excitatory postsynaptic potentials after a Ն30-min application. In isolated SCGNs, LEV pretreatment (Ն1 h) but not short-term application (5 min) significantly inhibited whole-cell Ba 2ϩ current (I Ba ) amplitude. In currentclamp recordings, LEV reduced the amplitude of the afterhyperpolarizing potential in a Ca 2ϩ -dependent manner but also increased the action potential latency in a Ca 2ϩ -independent manner, which suggests additional mechanisms associated with reduced excitability. Intracellular LEV application (4 -5 min) caused rapid inhibition of I Ba amplitude, to an extent comparable to that seen with extracellular LEV pretreatment (Ն1 h). Neither pretreatment nor intracellular application of UCB L060 produced any inhibitory effects on I Ba amplitude. These results identify a stereospecific intracellular pathway through which LEV inhibits presynaptic Ca V channels; resultant reductions in neuronal excitability are proposed to contribute to the anticonvulsant effects of LEV.

show abstract

Section: Tablesupporting

confidence: 86%

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway

Vogl¹,

Mochida²,

Wolff³

et al. 2012

Mol Pharmacol

109

View full text Add to dashboard Cite

show abstract

“…[11] Levetiracetam also regulates the influx of calcium into the cells, and modulates membrane depolarization and prevents irreversible cellular damage. [31][32][33] In this present study we determined the protective antioxidant effects of LEV on hepatic fibrosis. Significant increases were detected in the serum levels of GSH and TAC while there was a significant decrease in the serum levels of MDA in the LEV+STZ group.…”

Section: Discussionmentioning

confidence: 97%

Effect of levetiracetam on hepatic fibrosis in diabetic rats

Uyanıkgil

Akman

Çavuşoğlu³

et al. 2015

FNG & Bilim Tıp Dergisi

View full text Add to dashboard Cite

Objectives: In our study we investigated the possible effects of levetiracetam (LEV) on hepatic fibrosis in streptozotocin (STZ) induced diabetic rats with histopathology, real-time elastography imaging technique. We also aimed to investigate the effects of LEV on oxidative stress markers. Materials and methods: Diabetes was induced by intraperitoneal (i.p.) single dose injection of STZ (60 mg/kg). Twenty-one rats were randomly divided into three groups; control group, STZ group treated with 1 mL/kg/day saline (STZ+SP), and STZ group treated with 600 mg/kg/day LEV was administrated by i.p. for four weeks. All rats underwent a real-time elastography (strain-elasticity %). The liver sections are examined by histopathologically (liver fibrosis score). In addition, malondialdehyde, total antioxidant capacity, and glutathione levels were measured in plasma. Results: Treatment with LEV significantly decreased liver fibrosis score and increased strain measurement % on the real-time elastography in diabetic rats. In addition, treatment with LEV significantly increased total antioxidant capacity, glutathione and malondialdehyde levels decreased in plasma of diabetic rats. Conclusion: Levetiracetam has potential as a treatment for diabetic liver injury and hepatic fibrosis and can be a good candidate among new treatment options. In addition, real-time elastography is reliable imaging non-invasive technique for detecting hepatic fibrosis.Keywords: Diabetes mellitus; levetiracetam; oxidative stress; real-time elastography.Diyabetik sıçanlarda karaciğer fibrozisi üzerine levetirasetam etkisi ÖZ Amaç: Bu çalışmada, streptozotocin (STZ) ile indüklenmiş diyabetik sıçanlardaki hepatik fibrozis üzerine levetirasetamın (LEV) pozitif etkilerinin histopatolojik ve gerçek zamanlı elastografik görüntüleme tekniği ile incelenmesi amaçlandı. Yine bu çalışmada LEV'nin oksidatif stres belirteçleri üzerine etkisi araştırıldı. Gereç ve yöntemler: Diyabetik model, tek doz intraperitoneal (i.p.) STZ (60 mg/kg) enjeksiyonu ile yapıldı. Yirmi bir sıçan rastgele olarak üç gruba ayrıldı; kontrol grubu, STZ uygulaması yapılıp 1 mL/kg/gün salin verilen grup (STZ+SP) ve STZ uygulanıp dört hafta boyunca 600 mg/kg/gün i.p LEV uygulanan grup. Tüm sıçanlar gerçek zamanlı elastografik yöntem ile incelendi (gerilme-elastikiyet yüzdesi). Karaciğerden alınan kesitler histopatolojik olarak değerlendirildi (karaciğer fibroz skoru). Bunlara ek olarak, plazmadan malondialdehit, total antioksidant kapasite ve glutatyon seviyeleri ölçüldü. Bulgular: Levetirasetam ile tedavi edilen diyabetik sıçanlarda karaciğer fibroz skorlamasında anlamlı bir azalma ve gerçek zamanlı elastografik gerilim-elastikiyet yüzdesinde artış saptandı. Bununla birlikte LEV tedavisinde diyabetik sıçanlarda total antioksidant kapasitesinin arttığı, glutatyon ve malondialdehitin plazma seviyelerinin azaldığı görüldü. Sonuç: Levetirasetam, diyabetik karaciğer hasarı ve karaciğer fibrozisi için yeni tedavi seçenekleri arasında iyi bir aday olabilir. Buna ek olarak gerçek zamanlı elasto...

show abstract

“…Angehagen et al reported that LEV inhibits the caffeine-induced and Ca 2+ -dependent epileptiform discharges in hippocampal neuronal culture [34]. This drug also inhibits high potential-dependent calcium channels in conditions in vitro [35]. No effect of LEV on Na + and T-type Ca 2+ currents has been found [36].…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam protects hippocampal neurons in culture against hypoxia-induced injury

Sendrowski¹,

Boćkowski²,

Sobaniec³

et al. 2011

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Abstract:Many experimental studies indicate that some antiepileptic drugs possess neuroprotective properties in varied models of neuronal injury. Levetiracetam is a second-generation antiepileptic drug with a novel mechanism of action. In the present study, we evaluated the putative neuroprotective effect of levetiracetam on primary hippocampal cultures at seven day in vitro. Cell death was induced by incubation of neural cultures in hypoxic conditions over 24 hours. Neuronal injury was assessed by morphometric investigation of death/total ratio of neurons in light microscopy using Trypan blue staining and by evaluation of lactate dehydrogenase (LDH) release in the culture medium. Our results indicate that pre-conditioning of hippocampal cultures with high concentrations of levetiracetam (100 mM and 300 mM) protects neurons against hypoxia-induced death. Two-fold higher number of neurons remained viable as compared to control cultures without drug. Lack of neuroprotective action of the drug on hippocampal neural cultures was observed, when a low concentration (10 mM) of levetiracetam was used.

show abstract

Levetiracetam inhibits the high-voltage-activated Ca2+ current in pyramidal neurones of rat hippocampal slices

Cited by 196 publications

References 16 publications

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway

Effect of levetiracetam on hepatic fibrosis in diabetic rats

Levetiracetam protects hippocampal neurons in culture against hypoxia-induced injury

Contact Info

Product

Resources

About

Levetiracetam inhibits the high-voltage-activated Ca2+ current in pyramidal neurones of rat hippocampal slices

Cited by 196 publications

References 16 publications

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca2+ Channels through an Intracellular Pathway

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca2+ Channels through an Intracellular Pathway

Effect of levetiracetam on hepatic fibrosis in diabetic rats

Levetiracetam protects hippocampal neurons in culture against hypoxia-induced injury

Contact Info

Product

Resources

About

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway

The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca²⁺ Channels through an Intracellular Pathway