A PHARMACOLOGIC STUDY OF 5-ALLYL-5-²-CYCLOPENTENYL BARBITURIC ACID (CYCLOPAL)

¹ From The Research Laboratories, The Upjohn Co., Kalamazoo, Michigan

Cyclopal (5-allyl-5-²-cyclopentenyl barbituric acid) selected as the best of a series of cyclopentenyl barbiturates, has been compared with Pentobarbital U.S.P. in rats and dogs from the standpoint of acute and chronic oral toxicity, effectiveness and excretion.

The L.D.50/A.D.50 ratios for Cyclopal and Pentobarbital respectively were found to be 205/75 and 118/50 for rats and 105/27 and 65/18 for dogs. When dogs were given 50 per cent of the L.D.50 the onset of anesthesia was approximately one-half hour for both drugs. The duration of anesthesia at this dosage level was longer for Cyclopal (fourteen hours) than for Pentobarbital (five and one-half hours).

Using the minimum dose-response relationship as a criterion, both rats and dogs in the chronic study became somewhat refractory to Cyclopal and slightly susceptible to Pentobarbital. The degree of response, i.e., duration of "anesthesia", appeared in general to be related directly to the dose.

The quality of response was the same for both Cyclopal and Pentobarbital as judged by smoothness of onset of "anesthesia", depth of "anesthesia" and rapidity of recovery from hypnotic symptoms.

In dogs, absence of degenerative or pathological changes, normal liver function, general good health and normal deportment were observed at the end of five months of treatment with Cyclopal and Pentobarbital (A.D. 100 on alternate days).

Hypnotic material excreted in the urine of dogs receiving doses as large as the L.D.50 does not amount to more than 2.5 per cent of the ingested Cyclopal or Pentobarbital.