Abstract
A number of papers have been presented in support of the concept that epinephrine potentiates barbiturate anesthesia in experimental animals (1-3). Recently, Mazel et al. (4) reported that epinephrine increased the brain level of barbital above controls and suggested that epinephrine may affect the permeability of the blood-brain barrier as well as other barriers. However, mechanism of the potentiating action of epinephrine on barbiturate anesthesia still remained to be elucidated.
Meanwhile, Ohshika in our laboratory has reported that thiopental bound to plasma albumin can be displaced in vitro by a series of fatty acids (5) and further that anesthetic effect of thiopental was potentiated in rats or mice pretreated with sodium oleate. From a consideration of the results, he suggested the implication of plasma free fatty acids (FFA) in the thiopental anesthesia.
Several studies (6-8) have demonstrated that the pharmacological effect of a highly bound drug may be increased when the drug is displaced from its binding sites by another drug or substance. Solomon et al. (7) reported that many acidic compounds of unrelated chemical structure bound to a common site on the albumin molecule and that, among them, fatty acids were avidly bound to albumin and acted as effective displacers of another acidic drugs from albumin.
The well-known relation of epinephrine to FFA in the movement of the latter in and out of adipose tissue (9, 10) and the implication of epinephrine in barbiturate anesthesia suggested a trial of epinephrine under conditions similar those described for fatty acids.
The purpose of this investigation was to study the potentiating effect of epinephrine, and by comparison, sodium oleate on the thiopental anesthesia. The data presented here indicate that potentiation of thiopental anesthesia may be due to an increased penetration of thiopental into the brain. In addition, observations are also presented indicating that epinephrine may potentiate thiopental anesthesia through its lipolytic action.
