Differential effects of phenobarbital and pentobarbital on isolated nervous tissue

Epileptiform after discharges evoked by repetitive electrical stimulation of chronically isolated cortical slabs (cat) were shortened by low doses of phenobarbital but not affected by hypnotic doses of pentobarbital. Both pentobarbital and phenobarbital raised threshold and lowered spike amplitude in isolated sciatic nerves. The action of both drugs was increased by reducing Na in the medium and by decreasing the Ringer's pH. Similar to the action of other general anesthetics, the axonal effect of pentobarbital was enhanced by D2O replacement for H2O in the Ringer's (suggesting that tissue water is involved in pentobarbital action), whereas D2O replacement did not modify the action of phenobarbital or of local anesthetics. These results suggest that the varying in vivo effects of pentobarbital and phenobarbital may be due to a difference in their action upon excitable membranes (rather than to a different regional distribution in brain).