PURPOSE: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy. METHODS: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves. RESULTS: LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed. CONCLUSIONS: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.
PURPOSE: The anticonvulsant effects of the novel antiepileptic drug (AED) levetiracetam (LEV) were tested in neocortical slice preparations from 23 patients who underwent surgery for the treatment of refractory epilepsy. METHODS: Slices were used to evaluate the effects of LEV on two different models of epilepsy: low-Mg2+-induced untriggered and bicuculline-evoked stimulus-triggered epileptiform burst discharges and spontaneously appearing rhythmic sharp waves. RESULTS:LEV (0.1-1 mM) did not influence spontaneously appearing rhythmic sharp waves or Mg2+-free aCSF-induced epileptiform field potentials. LEV affected neither the amplitudes or duration nor the repetition rates of burst discharges in these epilepsy models. However, LEV (100-500 microM) significantly suppressed the ictal-like discharges elicited by the gamma-aminobutyric acid subtype A (GABAA)-receptor antagonist bicuculline. A marked reduction of the amplitude and duration of bicuculline-evoked field response in the presence of LEV was observed. CONCLUSIONS: The results indicate the potential for LEV to inhibit epileptiform burst discharges in human neocortical tissue, which is consistent with its effects in animal models of epilepsy. These results also support the seizure reduction observed in clinical trials and support that this may, in part, be related to the ability of LEV to inhibit epileptiform discharges.
Authors: Martin N Stienen; Aiden Haghikia; Hannes Dambach; Jan Thöne; Martin Wiemann; Ralf Gold; Andrew Chan; Rolf Dermietzel; Pedro M Faustmann; Daniel Hinkerohe; Nora Prochnow Journal: Br J Pharmacol Date: 2011-01 Impact factor: 8.739
Authors: Nora Sandow; Simon Kim; Claudia Raue; Dennis Päsler; Zin-Juan Klaft; Leandro Leite Antonio; Jan Oliver Hollnagel; Richard Kovacs; Oliver Kann; Peter Horn; Peter Vajkoczy; Martin Holtkamp; Heinz-Joachim Meencke; Esper A Cavalheiro; Fritz Pragst; Siegrun Gabriel; Thomas-Nicolas Lehmann; Uwe Heinemann Journal: Front Neurol Date: 2015-02-18 Impact factor: 4.003
Authors: Natalie L M Cappaert; Taco R Werkman; Nuria Benito; Menno P Witter; Johannes C Baayen; Wytse J Wadman Journal: Brain Behav Date: 2016-04-15 Impact factor: 2.708