Some Aspects of the Pharmacology of Apomorphine Hydrochloride.

Abstract

In spite of many chemical and pharmacological studies of apomorphine during the past 50 years, there still seems to be considerable doubt as to whether or not the green coloration which appears in apomorphine solutions is evidence of deterioration or of the formation of a new toxic substance. Guinard, 1 Eggleston and Hatcher 2 found little change pharmacologically in solutions of apomorphine which had become a deep green. Heinekamp, 3 however, believed that such apomorphine solutions were definitely less potent. The United States Pharmacopoeia X, and some text books (e. g., Trendelenburg 4 ) recommend that solutions should not be used, especially if green immediately or shortly after the dissolving of the solid drug. Harnack 5 declared that the oxidation with subsequent loss of potency occurred with some apomorphine preparations and not with others. The experiments reported below were, therefore, in part, undertaken to determine the effect of oxidation of the dissolved drug (as shown by the green color of the solution) upon its pharmacological characteristics.

Three different crystalline preparations∗ of apomorphine hydrochloride were used for making both the new and the old solutions which were injected into 7 healthy unanesthetized dogs of from 7 to 11 kilos for 1 to 4 1/2 months. Four of the 7 animals were injected daily for at least 4 months. The procedure finally adopted was to inject the animals once daily. Fresh solutions and green aged solutions of a given sample of apomorphine were administered on alternate days, subcutaneously. The minimal effective dose of 0.15 to 0.20 mg. per kilo was found to be the same as that reported by Eggleston and Hatcher. The data in Table I are representative of the results with injections over a period of 3 or 4 months.