MacDonald J F, Barker J L
Brain Res. 1982 Aug 26;246(2):257-64. doi: 10.1016/0006-8993(82)91173-8.
Intracellular recordings from mouse spinal neurons grown dissociated in tissue culture were used to study the effects of the water soluble benzodiazepine, flurazepam, upon neuronal excitability. Low concentrations of this drug (1 pM to 10 nM) depressed excitability in three distinctly different ways: (1) by directly increasing Cl- conductance, (2) by potentiating responses to GABA, and (3) by elevating spike threshold and/or depressing repetitive spike firing. Bathing neurons with picrotoxin induced 'convulsive-like' activity which was attenuated by flurazepam. The direct effects of flurazepam on the passive and active properties of membrane excitability were insensitive to picrotoxin. However, when the dose of flurazepam was increased to 10 nM or greater this drug lost its effectiveness. These results show that flurazepam is a potent drug with multiple sites of action all of which are likely to contribute to its pharmacological actions in vivo.
利用在组织培养中解离生长的小鼠脊髓神经元进行细胞内记录，以研究水溶性苯二氮䓬氟西泮对神经元兴奋性的影响。低浓度的这种药物（1皮摩尔至10纳摩尔）以三种明显不同的方式抑制兴奋性：（1）通过直接增加氯离子电导，（2）通过增强对γ-氨基丁酸（GABA）的反应，以及（3）通过提高动作电位阈值和/或抑制重复动作电位发放。用荷包牡丹碱浸泡神经元会诱发“惊厥样”活动，而这种活动会被氟西泮减弱。氟西泮对膜兴奋性的被动和主动特性的直接影响对荷包牡丹碱不敏感。然而，当氟西泮的剂量增加到10纳摩尔或更高时，这种药物就失去了效力。这些结果表明，氟西泮是一种具有多个作用位点的强效药物，所有这些位点都可能对其体内药理作用有贡献。
