Acute effects of gamma-vinyl-GABA on low-magnesium evoked epileptiform activity in vitro.
Vigabatrin (gamma-vinyl-GABA, VGB) is a gamma-aminobutyric acid (GABA) derivative designed to boost synaptic inhibition by inhibiting the degradation of GABA in brain tissue. Indeed, VGB shows potent anti-convulsant activity in animal models of epilepsy and in humans with complex partial seizures. However, details of the mechanism of action of VGB are not well understood and the systemic effects include possible pro-convulsant actions. We therefore analysed the effects of VGB in rat brain slices in the low-Mg(2+) model in vitro. VGB at 100 microM-5 mM showed a concentration- and time-dependent reduction of interictal-like events in the hippocampal CA1 region. Likewise, VGB suppressed epileptiform discharges in the medial entorhinal cortex (mEC), which are known to resist conventional anti-convulsants. In contrast, evoked population spikes in CA1 (which became repetitive after washout Mg(2+)) were not altered by VGB. Our data show that VGB is efficient against epileptiform discharges in temporal structures including pharmacoresistant patterns of activity. The waveform of evoked population spikes in this in vitro model is no indicator for the anti-convulsant properties of drugs.
Engel
D
D
Johannes-Müller-Institut für Physiologie der Charité, Tucholskystr. 2, 10117, Berlin, Germany.
Endermann
U
U
Frahm
C
C
Heinemann
U
U
Draguhn
A
A
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004827:Epilepsy / Q000188:drug therapy / Q000209:etiology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008274:Magnesium / Q000008:administration & dosage; D008297:Male; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D020888:Vigabatrin / Q000494:pharmacology*
D000927:Anticonvulsants; D020888:Vigabatrin; D008274:Magnesium