Draguhn A, Jungclaus M, Sokolowa S, Heinemann U
Institut für Physiologie der Charité, Abteilung Neurophysiologie, Berlin, Germany.
Eur J Pharmacol. 1997 May 1;325(2-3):245-51. doi: 10.1016/s0014-2999(97)00121-0.
Losigamone is a new antiepileptic drug with an unknown mechanism of action. Here we report on the effects of losigamone on the synaptic activity in a network of cultured rat hippocampal neurons. Losigamone dose dependently reduced the frequency of spontaneous synaptic events without affecting the mean current amplitude. The drug affected equally the isolated inhibitory as well as excitatory postsynaptic currents. Miniature postsynaptic currents were not altered by losigamone, suggesting that the mechanism of action depends on functional Na+ channels. Consistent with these findings, the drug decreased the frequency of spontaneous action potentials and suppressed repetitive firing of neurons. Thus, losigamone generally depresses synaptic activity in a neuronal network without selectively modulating a specific postsynaptic receptor type. We conclude that losigamone acts via a presynaptic mechanism reducing neuronal excitability.
洛西加莫是一种作用机制不明的新型抗癫痫药物。在此，我们报告洛西加莫对培养的大鼠海马神经元网络中突触活动的影响。洛西加莫剂量依赖性地降低自发突触事件的频率，而不影响平均电流幅度。该药物对孤立的抑制性和兴奋性突触后电流的影响相同。微小突触后电流不受洛西加莫影响，这表明其作用机制取决于功能性钠离子通道。与这些发现一致，该药物降低了自发动作电位的频率，并抑制了神经元的重复放电。因此，洛西加莫通常会抑制神经元网络中的突触活动，而不选择性地调节特定的突触后受体类型。我们得出结论，洛西加莫通过一种减少神经元兴奋性的突触前机制发挥作用。
