Levetiracetam reduces caffeine-induced Ca2+ transients and epileptiform potentials in hippocampal neurons.
The effect of the novel antiepileptic drug levetiracetam on caffeine (10 mM)-induced intracellular calcium ([Ca2+]i) response was investigated in rat hippocampal neurons in culture, with the aim of exploring the cellular mechanisms of this new drug. Levetiracetam significantly reduced caffeine-induced [Ca2+]i) response, with maximum inhibition at 32 microM. The R-enantiomer of levetiracetam, ucb L060, which is devoid of anticonvulsant activity, at 32 microM had no effect on caffeine-induced [Ca2+]i) response. Caffeine 10 mM also induced epileptiform field potentials in rat hippocampal slices : single stimuli evoked repetitive population spikes and spontaneous field bursts regularly occurred. Levetiracetam (32 microM) significantly inhibited the amplitudes and the number of caffeine-induced repeated population spikes and delayed the appearance of spontaneous bursts, while ucb L060 (32 microM) completely lacked anti-caffeine activity. These results suggest that the inhibition of caffeine-induced Ca release from intra-neuronal stores might be an excitability-reducing effect of levetiracetam, contributing to its antiepileptic activity.
Angehagen
Mikael
M
Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden.
Margineanu
Doru Georg
DG
Ben-Menachem
Elinor
E
Rönnbäck
Lars
L
Hansson
Elisabeth
E
Klitgaard
Henrik
H
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D000077287:Levetiracetam; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000927:Anticonvulsants; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000077287:Levetiracetam; D002118:Calcium; D010889:Piracetam