Synthetic Ephedrine. ∗

Abstract

Ephedrine was successively synthesized by Nagai, 1 Späth and Göhring, 2 and Eberhard. 3 The chemical difference between the ephedrine occurring naturally and that prepared synthetically lies in their optical activity, the natural being laevo-rotatory while the synthetic is optically inactive. From the pharmacological point of view, one would expect synthetic ephedrine to possess an action similar to that of the natural product but to be less potent; for it is known that the racemic form of several well known substances, notably hyoscyamine, hyoscine, homatropine, and epinephrine is weaker than the l-form. 4 After the recent demonstration of the action and clinical uses of the ephedrine isolated from the Chinese medicinal herb Ma Huang, investigators studied the synthetic ephedrine, and showed its comparable effects to those of the natural product. 5 , 6 , 7 , 8 , 9 , 10 , 11

The present work consists of a comparison, both qualitative and quantitative, of the natural ephedrine prepared under the supervision of the author in 1924, and the synthetic ephedrine courteously supplied by E. Merck of Darmstadt, Germany. Its trade name is ephetonine. A preliminary clinical trial is also included. The hydrochloride of the synthetic compound melts at 187° C., is optically inactive, in aqueous solution at 21° C., and gives with cupric hydroxide a purple color extractable by ether, 12 It is apparently stable to light, air and heat.

When applied locally to the conjunctival sac of rabbits and man, synthetic ephedrine produces mydriasis with the preservation of the light reflex. An intravenous injection of the solution in the dosage of 2 mg. per kg. in anesthetized dogs, cats, or rabbits, results in a prolonged rise of arterial blood pressure, lasting for 25 to 30 minutes or longer, much the same as that seen after a similar injection of the natural ephedrine.