Abstract

The effects of pH on the potency of pentobarbital in blocking the action potential have been studied with internally and externally perfused squid giant axons. Pentobarbital exhibits stronger blocking action at low pH than at high pH when applied externally or internally at different pH values. In these experiments the pH of the phase opposite to that in which the drug was applied was maintained constant. When compared at the same pH, the blocking potency is higher with internal application of pentobarbital than with external application. However, when applied either externally or internally at a constant pH, the blocking potency is independent of the pH in the opposite phase. These observations, when compared to the theoretical calculations of the possible active forms, support the concept that the uncharged molecular form is responsible for the blocking action.