ANALGESIC POTENCY AND SIDE ACTION LIABILITY IN MAN OF HEPTAZONE, WIN 1161-2, 6-METHYL DIHYDROMORPHINE, METOPON, LEVO-ISOMETHADONE AND PENTOBARBITAL SODIUM, AS A FURTHER EFFORT TO REFINE METHODS OF EVALUATION OF ANALGESIC DRUGS

¹ The Anesthesia Laboratory of the Harvard Medical School at the Massachusetts General Hospital, Boston, Massachusetts

1. Our method for the determination of the analgesic potency of new drugs in man has been applied to four drugs. It is shown how by this method an accurate estimate of analgesic potency can be obtained with an economy of patients. Sixty milligrams of Heptazone (dl 4,4-diphenyl-6-morpholino-heptanone-3-hydrochloride), 30 mgm. of 6-methyl dihydromorphine, and 3.5 mgm. of Metopon (methyl dihydromorphinone hydrochloride) all produce analgesia in man equivalent to 10 mgm. of morphine. These drugs were given subcutaneously on the basis of body weight.

2. WIN 1161-2 (l-3-dimethylamino-1,1-diphenylbutyl ethyl sulfone hydrochloride) is unsuited for clinical use because it undergoes hydrolysis at sterilization temperature. The interest here is the fact that this finding strongly supports the validity of our method, since it was made while the drug was believed to be stable.

3. The side action liability of equivalent analgesic doses of these drugs as well as 10 mgm. of l-isomethadone and 200 mgm. of pentobarbital sodium were studied in normal subjects.

4. Except for l-isomethadone, no drug studied possessed advantages over morphine. Ten milligrams per 70 kgm. of body weight of l-isomethadone produced fewer symptoms (nausea and vomiting) than morphine. Its effects on respiration were similar to morphine.

5. Pentobarbital sodium in large dose produced marked psychic effects but little depression of respiration.

6. The future of studies of new analgesic drugs is discussed.