A COMPARATIVE STUDY ON HYPNOTICS OF THE BARBITURIC ACID SERIES

¹ From the Pharmacologic Department of the Abbott Laboratories, Chicago, Illinois

Preliminary experiments with eight hypnotics of the series on cats and dogs showed that both of these animals are unsatisfactory for comparative tests on the barbituric acid series, because administration is cumbersome, reaction slow, and a standard of reaction difficult to establish. Accordingly, the albino rat was tried, and found to react readily and with sufficient constancy to the members of this series.

The toxicities and efficiencies of sixteen members of the barbituric acid series were determined for the albino rat. The index of safety for each hypnotic tested was expressed as the difference between its minimum fatal dose and minimum effective dose in percentage of its minimum fatal dose.

In order of increasing toxicity these barbituric acid derivatives were found to rank as follows: di-n-butyl, di-ethyl (Barbital), n-butyl allyl, n-butyl ethyl (Neonal), ethyl allyl, n-propyl allyl, iso-butyl allyl, iso-amyl allyl, n-butyl iso-propyl, di-allyl (Dial), iso-amyl ethyl (Amytal), phenyl ethyl (Luminal), iso-propyl allyl (the hypnotic agent in Allonal), iso-propyl ethyl, sec.-butyl allyl.

In order of increasing efficiency: di-ethyl (Barbital), di-n-butyl, phenyl ethyl (Luminal), ethyl allyl, iso-propyl ethyl, iso-amyl allyl, n-butyl allyl, n-butyl iso-propyl, n-propyl allyl, n-butyl ethyl (Neonal), d-allyl (Dial), iso-amyl ethyl (Amytal), iso-propyl allyl (the hypnotic agent in Allonal), iso-butyl allyl, sec.-butyl allyl.

In order of increasing safety margin: iso-propyl ethyl, phenyl ethyl (Luminal), di-ethyl (Barbital), ethyl allyl, di-n-butyl, iso-amyl allyl, n-butyl iso-propyl, iso-propyl allyl (the hypnotic agent in Allonal), sec.-butyl allyl, n-propyl allyl, iso-amyl ethyl (Amytal), di-allyl (Dial), n-butyl ethyl (Neonal), iso-butyl allyl, n-butyl allyl.