Potency of Barbiturates in Inhibition of Frog Gastric Secretion

Abstract

Previously Saidman et al. (1) found a correlation between anesthetic potency and the oil/gas partition coefficient. Their measure of potency was the MAC, i.e., the minimum anesthetic concentration required to prevent a muscular response to a skin incision in 50% of the subjects to whom the anesthetic was administered. Schwartz and MacKrell (2) showed that the percentage of anesthetic needed to produce a given decrease in the H⁺ secretory rate of frog gastric mucosa in vitro was proportional to the MAC in man and on this basis predicted the MAC values for chloroform and Compound 347 (Ethrane). These results suggested lipid solubility as a factor influencing the potency of anesthetics in inhibition of acid secretion.

In the work above (2) on frog gastric mucosa the anesthetics had molecules with no more than four carbon atoms. Mullins (3) points out that for compounds with more than four carbon atoms the anesthetic potency declines and that by the time one reaches a compound of C₁₀ or C₁₂ an anesthetic series is inert and higher analogues, whether they be alcohol, ether, or paraffin, have no anesthetic activity. Hence it is inferred that there is a site size limit for anesthetic molecules in biological membranes. In contrast, other investigators (4) found that the hypnotic activity of narcotics such as barbiturates was closely related to their relative lipophilic character as defined by the logarithm of the octanol-water partition coefficient, log P. Consequently, it was of interest to compare the behavior of barbiturates with anesthetics under similar conditions, namely, their effects on frog gastric mucosa. The question then is: to what extent is lipid solubility of barbiturates as defined by log P indicated as a factor in inhibition of acid secretion.