A TOXICOLOGICAL AND PHARMACOLOGICAL INVESTIGATION OF SODIUM SEC-BUTYL ETHYL BARBITURIC ACID (BUTISOL SODIUM)

¹ From the Department of Pharmacology, Jefferson Medical College, Philadelphia

1. The intravenous LD₅₀ for sodium sec-butyl ethyl barbiturate for dogs, rabbits and albino rats was found to be 90, 91 and 70 mg. per kg. respectively. The intraperitoneal doses for rabbits, albino rats and white mice are 95, 70 to 76, and 247 mg. per kg. respectively. The oral dose for rabbits is 194 and for rats 78 mg. per kg.

2. The intravenous LD₅₀ for rabbits for phenobarbital sodium is 185 mg. per kg. and the intraperitoneal doses for rats and mice are 190 and 340 mg. per kg. respectively.

3. The intraperitoneal LD₅₀ for pentobarbital sodium in rats weighing 124 gm. is 75 and in those weighing 185 gm. it is 48 mg. per kg. (supporting Fitch and Tatum (4) but not Carmichael (5)). In mice it is 140 mg. per kg.

4. The intraperitoneal LD₅₀ for barbital sodium in white mice is 763 mg. per kg.

5. The intraperitoneal LD₅₀ for sodium ethyl n-butyl barbiturate in albino rats is 197 mg. per kg.

6. The duration of action of sodium sec-butyl ethyl barbiturate is dependent upon the total amount of the drug injected and upon the size, health and species of animal used. Of the animals used in this study it is longest in the dog.

7. For the three species of animals employed the barbiturates which we studied can be arranged in the following order according to their durations of action: Mouse, (1) pentobarbital sodium; (2) sodium sec-butyl ethyl barbiturate; (3) barbital sodium; (4) phenobarbital sodium. Albino rat, (1) n-hexyl ethyl; (2) ethyl (1 methyl butyl); (3) phenyl ethyl; ethyl n-butyl; sec-butyl ethyl; (4) propyl-methyl-carbinyl allyl. Rabbit, (1) ethyl (1-methyl butyl), propyl-methyl-carbinyl allyl; (2) sec-butyl ethyl; (3) iso-amyl ethyl; (4) phenyl ethyl.

8. A large dose of sodium sec-butyl ethyl barbiturate rapidly injected intravenously will produce either marked slowing or even permanent cessation of respiration. The heart continues to beat some minutes longer.

9. Administration of sodium sec-butyl ethyl barbiturate will cause a fall in arterial blood pressure. The extent of the fall is dependent upon the amount given and the speed of injection or absorption.

10. If the fall in blood pressure is not extensive it is accompanied by an increase in the volume of the spleen, limb, kidney and ear. This vasodilator action is due to a direct effect of the drug on the vessel wall.

11. Sodium sec-butyl ethyl barbiturate, as far as could be determined, produces no change in cardiac rhythm such as is seen in the dog following sodium thiopentobarbital.

12. The excised as well as the intact intestine is depressed by sodium secbutyl ethyl barbiturate. In the excised intestine its depressant effect is somewhat greater than that of phenobarbital sodium but less than that produced by pentobarbital sodium.

13. Excised uterine segments of rabbits, cats and guinea pigs are depressed by this barbiturate.

14. No gross changes in the liver and other organs were noted after a prolonged series of administrations of the drug with rest intervals between.

15. No significant difference was found in the duration of action of the drug in normal and nephrectomized dogs. it is assumed therefore that the drug is destroyed somewhere in the body and partly excreted in the urine only when given in excessive doses.