Comparison of the action of different barbiturates on squid axon membranes

Experiments utilizing squid giant axons have been carried out to determine if the duration of anesthesia obtained from phenobarbital, pentobarbital and hexobarbital can be explained by events related to their action at the nerve membrane level. For comparison, the barbiturates were perfused both outside and inside the squid axon at concentrations which produced an approximately equivalent depression of the maximum rate of rise of the action potential. The time to 50% maximum block and the time to 50% maximum recovery following washing, were compared for all three drugs. All three barbiturates were more potent from inside the squid axon than from the outside. This finding coupled with the fact that the time course of the drug effects was much shorter when applied inside as compared to outside suggests an internal site of action. There was no statistically significant difference between a short acting barbiturate and a long acting barbiturate with respect to their time course of action or recovery when they were both applied to either the inside or outside of the membrane.