STUDIES OF TWO NEW SUBSTITUTED VINYL BARBITURIC ACIDS

¹ From the Laboratory of Pharmacology, University of Pennsylvania, and the Department of Medicine, Duke University School of Medicine

1. Pharmacologic studies of two selected members of the new series of substituted vinyl barbituric acids have been described. The compounds studied are 5-ethyl 5-(1-methyl 1-butenyl) barbituric acid (compound 37) and 5-propyl 5-(1-methyl 1-butenyl) barbituric acid (compound 92). Their actions were compared to those of isoamylethyl barbituric acid.

2. The new compounds are potent narcotics. The margin of safety in rats and dogs is comparatively wide, there being a tendency toward higher values of the LD 50/AD 50 ratio for the new compounds than for isoamylethyl barbituric acid.

3. Rats and dogs which received approximately minimum anesthetic doses of the new compounds three times weekly for twelve and eleven weeks, respectively, showed no gross or microscopic lesions which could be related to the drugs.

4. Compound 37 was quite uniform in its narcotic effect in the above animals. Compound 92 was less consistent and there was evidence of the development of tolerance to it in rats.

5. The new compounds were considerably less depressant to blood pressure upon intravenous injection in dogs than was isoamylethyl barbituric acid. This also was true of compound 37 after intraperitoneal injection in dogs.

6. Evidence was obtained indicating less profound depression of the respiratory center in decerebrate dogs from narcotic doses of compound 37 than from equivalent amounts of isoamylethyl barbituric acid.

7. The oxygen utilization of white rats decreased after the administration of all three barbituric acids tested. No significant difference between the compounds in their effect on basal metabolism was observed.

8. Only negligible amounts of narcotic material have been found in the urine of dogs following anesthetic doses of compound 37.

9. Sodium 5-ethyl 5-(1-methyl 1-butenyl) barbiturate (compound 37) has been administered in doses of 0.032 to 0.2 gram ( to 3 grains) as a sedative and hypnotic to more than 100 patients with good results and without toxic reactions. The action of the compound was gradual during induction; relatively brief in duration, and there was notable absence of after-effects following its use.