Some Reactions of Ammonolyzed Epinephrine

Abstract

Previous work 1 on certain nitrogenous substances in liquid ammonia has shown that some of them tend to ammonolyze with changes in their physical, chemical, and biological properties. Ammonolyzed edestin was reported 2 not to have given an anaphylactic reaction with a guinea pig previously sensitized to the untreated edestin. Recent observations on changes in some physical constants of certain amino acids in liquid ammonia indicate an ammonolysis. Epstein, Gunn and Virden 3 have shown changes brought about in the physiological activity of phenylethylamines by methylation. These facts, in addition to the observations of Kraus and White 4 that the hydroxyl groups of alcohols and phenols are quite reactive in liquid ammonia and to the report of Roberts and Miller 5 that the phenolic group of tyrosine seems to be acidic in liquid ammonia have led us to believe that epinephrine could be ammonolyzed and thus altered in its physiological activity.

The chemical treatment consisted of adding 60 mg. of Parke, Davis adrenalin to 150 cc. of liquid ammonia contained in a Dewar flask connected by gas-tight stoppers and tubing to a mercury seal allowing the ammonia to vaporize without admitting moisture to the adrenalin. The liquid ammonia, previously dried over sodium by the method of Fernelius and Johnson, boils off in about 24 hours, and the drug is ready for use. The yellowish adrenalin base darkens to a reddish-brown on standing in liquid ammonia, and its solubility in water and in glycerine decreases.

The flaky material is powdered, and used in the form of an aqueous sol. With glycerine used as a vehicle, the suspension is more uniform, and the base has less tendency to settle out. When water is used, the injection is made at once since the ammonolyzed base hydrolyzes on standing. With glycerine, a pressor activity characteristic of the new compound was obtained after 30 days, but after standing for 6 months an adrenalin curve was again obtained on injection.