Sodium Propyl-methyl-carbinyl Allyl Barbiturate,a Short Acting Hypnotic

Abstract

Fitch, Waters, and Tatum 1 in their extensive work on barbituric acid hypnotics emphasized the importance of employing short acting members for surgical procedures. Among the different derivatives synthesized by Shonle and his associates, 2 , 3 , 4 the sodium salt of propyl-methyl-carbinyl allyl barbituric acid appears to have the desirable promptness and brevity of action. The same compound has been prepared by Tabern and Volwiler. 5

By following Eddy's scheme of recording results, 6 it was found that in rats by intraperitoneal injection the minimal anesthetic dose (M.A.D.) was 40 mg. and the minimal lethal dose (M.L.D.) 110 mg., per kg. Twenty mg. per kg. by the same route of administration were sufficient to induce sleep. These animals, 220 in number, weighed on the average 94 gm. In dogs by intravenous injection of a 5% solution at the rate of 1 cc. per minute, the M.A.D. was ascertained to be 25 mg. and the M.L.D. 50 mg., per kg. By mouth in the same species of animal the M.A.D. was determined to be 35 mg. and the M.L.D. 90 mg., per kg. A total of 83 dogs were used.

A comparison of the onset and duration of action of sodium propyl-methyl-carbinyl allyl barbiturate in dogs with those of sodium amytal and pentobarbital sodium is shown in Table I. It will be noted that when given by mouth the appearance of ataxia occurred slightly sooner with the new barbituric acid derivative. Its duration of anesthesia was, on the average, longer than that with pentobarbital sodium and comparable to that with sodium amytal. However, the time for complete recovery after the administration of sodium propyl-methyl-carbinyl allyl barbiturate was approximately half that with sodium amytal, and slightly shorter than that with pentobarbital sodium.

Similar to sodium amytal and pentobarbital sodium, the new compound by intravenous injection proved to protect rabbits from 4 but not 5 M.L.D.'s of strychnine or cocaine—34 animals being employed for this purpose.