THE EFFECTS OF THIOPENTAL SODIUM, CHLOROFORM, AND DIETHYL ETHER ON THE METABOLISM AND TOXICITY OF PROCAINE

¹ Department of Biochemistry and Pharmacology, Indiana University, Indianapolis, Indiana

1. Doses of procaine hydrochloride of 0.3 mgm./kgm./min. may be given intravenously without any anesthesia, but doses of 1 mgm./kgm./min. require anesthesia.

2. Thiopental sodium is without influence on the rate of destruction of procaine by the liver in vitro, and it has no influence on the blood levels of procaine and p-aminobenzoic acid in the intact animal.

3. Livers from dogs anesthetized with chloroform hydrolyze procaine more slowly than the controls. Blood levels of procaine are higher in the intact dogs anesthetized with chloroform than in the dogs anesthetized with thiopental sodium, when the same dose is given.

4. Livers from dogs anesthetized with diethyl ether hydrolyze procaine at the same rate as the livers from dogs anesthetized with chloroform. The blood levels of procaine in intact dogs anesthetized with ether are higher than in the dogs anesthetized with chloroform, when the dosage is the same.

5. Lethal levels of procaine in venous blood are 7.6 mgm./100 cc. for dogs anesthetized with thiopental sodium, 6.8 mgm./100 cc. for dogs anesthetized with chloroform, and 3.5 mgm./100 cc. for dogs anesthetized with diethyl ether.

6. The difference in the fatal doses of procaine for dogs anesthetized with chloroform and those anesthetized with thiopental sodium may be accounted for by the effect of chloroform on the liver since the difference in blood levels is probably not significant. The greater toxicity of procaine with diethyl ether is only partly accounted for by the effect on liver as shown by a significant difference in blood levels of procaine.