Shrivastav B B
J Pharmacol Exp Ther. 1977 Apr;201(1):156-61.
The active form of ketamine has been studied with internally perfused squid qiant axons. The drug was applied internally, and decreases in peak transient and steady-state conductances as measured by voltage clamp technique were taken as an index of activity. When the total internal ketamine concentration was maintained constant, the suppression peak transient and steady-state conductances decreased with an increase in internal pH from 7.0 TO 8.4. When the concentration of the internally present charged form of ketamine was kept constant, the suppression of the peak transient conductance remained almost constant at internal pH values of 7.0, 7.3 and 7.7, but increased at pH 8.4. However, the suppression of the stead-state conductance became more prominent as the pH was raised from 7.0 to 8.4. With a constant internal concentration of the uncharged form, the suppression of both conductances decreased as the pH was raised from 7.0 to 8.4. Computation of dissociation constants to suppretamine is more potent than the charged form at all internal pH values examined. These data also show that the potency to suppress the peak transient conductance by the charged and uncharged forms of ketamine decreased as the intertance of the charged form increased, and that of the uncharged form decreased considerably with increase in the internal pH.
已利用内部灌注的乌贼巨轴突对氯胺酮的活性形式进行了研究。该药物通过内部给药，通过电压钳技术测量的峰值瞬态电导和稳态电导的降低被用作活性指标。当内部氯胺酮总浓度保持恒定时，随着内部pH值从7.0升至8.4，对峰值瞬态和稳态电导的抑制作用减弱。当内部存在的带电形式的氯胺酮浓度保持恒定时，在内部pH值为7.0、7.3和7.7时，对峰值瞬态电导的抑制作用几乎保持恒定，但在pH值为8.4时增加。然而，随着pH值从7.0升高到8.4，对稳态电导的抑制作用变得更加显著。在未带电形式的内部浓度恒定的情况下，随着pH值从7.0升高到8.4，两种电导的抑制作用均减弱。在所研究的所有内部pH值下，计算得出的去甲氯胺酮的解离常数表明其比带电形式更有效。这些数据还表明，氯胺酮的带电形式和不带电形式抑制峰值瞬态电导的效力随着带电形式含量的增加而降低，且不带电形式的效力随着内部pH值的升高而显著降低。
