Active form of ketamine in squid giant axons.

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.