A TOXICOLOGIC AND PHARMACOLOGIC INVESTIGATION OF CYCLOHEPTENYLETHYL BARBITURIC ACID (MEDOMIN)

¹ Departments of Pharmacology and Medicine, Jefferson Medical College, Philadelphia, Pennsylvania

1. The LD₅₀ of cycloheptenylethyl barbituric acid injected intraperitoneally is 284 mgm./kgm. for white mice, and 220 mgm./kgm. for albino rats. When the drug is injected intravenously the LD₅₀ is 119 mgm./kgm. for rabbits, and 105 mgm./kgm. for dogs.

2. Using the duration of induced sleep as the criterion, both rabbits and dogs develop a tolerance for cycloheptenylethyl barbituric acid.

3. Animals rendered tolerant to this barbiturate are also tolerant to pentobarbital sodium and vice versa.

4. Large doses of cycloheptenylethyl barbituric acid rapidly given intravenously produce a sudden fall in arterial blood pressure. The extent of fall is directly proportional to the amount given and to the speed of intravenous administration. An increased heart rate occurs during the fall and persists for some minutes after the blood pressure has returned to the control level.

5. Large intravenous doses of cycloheptenylethyl barbiturate given rapidly produce marked slowing, and may cause permanent cessation, of respiration in expiration. The respiratory mechanism fails before the heart.

6. In the experiments in which the fall in blood pressure is not extensive there appears to be a dilation of the vessels of the spleen, intestine, kidney and limb. In all of the experiments in which the fall in blood pressure is sudden and extensive a decrease in the volume of these organs is observed which we believe to be passive in character. The vessels of the skin dilate.

7. This barbiturate appears to have less depressant effect upon the cardiac vagus nerves than do other intermediate acting barbiturates such as amytal sodium and seconal sodium.

8. Like other intermediate acting barbiturates cycloheptenylethyl barbiturate is destroyed in the body and is excreted as the parent substance only when excessively large doses are given.