Johansen J, Kleinhaus A L
Brain Res. 1986 Jun 25;376(2):255-61. doi: 10.1016/0006-8993(86)90187-3.
Phenobarbital (PNB), pentobarbital (PTB) and methohexital (MTX) decreased the maximum rate of depolarization Vmax and duration of divalent cation action potentials elicited in leech nociceptive neurons in Na+-free solutions containing the K+-channel blocker TEA, without significantly affecting resting membrane potential or conductance. The block of the divalent cation action potentials was reversible and dose-dependent, ED50 for inhibition of Vmax being 560 microM for MTX, 800 microM for PTB and 3000 microM for PNB. This order of potency correlated well with the ratio of unchanged/charged form of the drugs at physiological pH suggesting that in leech, as in other preparations, the non-ionized form was the active one. In Na+-containing Ringer, the 3 barbiturates depolarized and decreased membrane resistance in the lateral nociceptive cells, but not the medial nociceptive cells. These results provide additional information regarding the newly described pharmacological differences among closely related neurons. These membrane actions may be related to some of the excitatory properties described for other barbiturates in invertebrate and mammalian preparations.
苯巴比妥(PNB)、戊巴比妥(PTB)和甲己炔巴比妥(MTX)降低了在含有钾通道阻滞剂四乙铵的无钠溶液中,水蛭伤害性神经元所引发的二价阳离子动作电位的最大去极化速率Vmax和持续时间,而对静息膜电位或电导没有显著影响。二价阳离子动作电位的阻断是可逆的且呈剂量依赖性,MTX抑制Vmax的半数有效剂量(ED50)为560微摩尔,PTB为800微摩尔,PNB为3000微摩尔。这种效力顺序与药物在生理pH下未变化/带电形式的比例密切相关,这表明在水蛭中,与其他制剂一样,非离子化形式是活性形式。在含钠的林格氏液中,这三种巴比妥酸盐使外侧伤害性细胞去极化并降低膜电阻,但对内侧伤害性细胞没有影响。这些结果提供了关于新描述的密切相关神经元之间药理学差异的更多信息。这些膜作用可能与在无脊椎动物和哺乳动物制剂中描述的其他巴比妥酸盐的一些兴奋特性有关。