Gorji Ali, Höhling Jorg-Michael, Madeja Michael, Straub Heidrun, Köhling Rüdiger, Tuxhorn Ingrid, Ebner Alois, Wolf Peter, Panneck H W, Behne F, Lahl Rainer, Speckmann Erwin-Joseph
Institut für Physiologie, Universität Münster, Münster, Germany.
Epilepsia. 2002 Dec;43(12):1480-7. doi: 10.1046/j.1528-1157.2002.23702.x.
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.
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.
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.
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.
在23例因难治性癫痫接受手术治疗的患者的新皮质切片标本中测试新型抗癫痫药物（AED）左乙拉西坦（LEV）的抗惊厥作用。
使用切片评估LEV对两种不同癫痫模型的作用：低镁诱导的无触发和荷包牡丹碱诱发的刺激触发癫痫样爆发放电以及自发出现的节律性尖波。
LEV（0.1 - 1 mM）不影响自发出现的节律性尖波或无镁人工脑脊液诱导的癫痫样场电位。在这些癫痫模型中，LEV既不影响爆发放电的幅度、持续时间，也不影响其重复率。然而，LEV（100 - 500 microM）显著抑制了γ-氨基丁酸A型（GABAA）受体拮抗剂荷包牡丹碱诱发的癫痫样放电。在存在LEV的情况下，观察到荷包牡丹碱诱发的场反应的幅度和持续时间明显降低。
结果表明LEV具有抑制人新皮质组织中癫痫样爆发放电的潜力，这与其在癫痫动物模型中的作用一致。这些结果也支持了在临床试验中观察到的癫痫发作减少，并支持这可能部分与LEV抑制癫痫样放电的能力有关。
