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Journal of Pharmacology And Experimental Therapeutics, Vol. 60, Issue 2, 125-142, 1937
Copyright © 1937 by American Society for Pharmacology and Experimental Therapeutics

A PHARMACOLOGIC STUDY OF CERTAIN THIOBARBITURATES

O. M. GRUHZIT 1, A. W. DOX 1, L. W. ROWE 1, and M. C. DODD 1

1 Research Laboratories, Parke, Davis and Company, Detroit, Michigan

1. Sulfur was substituted for oxygen in various barbituric acids. Six of the new thiobarbituric acids were found to possess anesthetic properties when administered intravenously, intraperitoneally, or perorally but little if any hypnotic or anesthetic effect when given intramuscularly or subcutaneously.

2. Isoamylethyl and (1-methylbutyl) ethyl thiobarbiturates induced deep anesthesia and showed respective ratios (M.T.D/M.A.D) of 7.5 and 4.5 intravenously in rats. In dogs comparative ratios were 4.5 and 3.8 respectively.

3. In comparable minimal anesthetic doses, 20 to 30 mgm. per kilogram of isoamylethyl thiobarbiturate and 10 to 15 mgm. per kilogram of (l-methylbutyl) ethyl barbiturate, the former was better tolerated, showed somewhat less depression of respiratory function and caused less severe pathologic changes in organs than the latter, i.e. the (1-methylbutyl) ethyl thiobarbiturate is about twice as toxic (45 mgm. per kilogram) as the isoamylethyl thiobarbiturate (90 mgm. per kilogram) but its effective anesthetic dose, as shown above, is only about one-half that of isoamylethyl thiobarbiturate.

4. Administration of thiobarbiturates intravenously induces almost instantaneous anesthesia, which is brief in duration and quiet in recovery.

5. Induction of anesthesia is accompanied by depression of respiratory function. Cardiac function in some animals is stimulated, in others it is depressed.

6. Anesthetic doses in animals, following intravenous administration, cause considerable congestion, stasis and often hemorrhages in lungs, liver, kidneys and central nervous system.

7. Two of the thiobarbituric acids studied [isoamylethyl and (1-methylbutyl) ethyl] possess satisfactory anesthetic power when given intravenously to animals and are capable of inducing surgical anesthesia. Their application for induction of anesthesia in human beings awaits the outcome of clinical studies now in progress.

Submitted on January 18, 1937




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