THE PHYSIOLOGICAL DISPOSITIONS OF ³H-SCOPOLAMINE AND ³H- Anisodine

Scopolamine and anisodine are alike in chemical structure, except that anisodine possesses a hydroxyl group on the α-carbon atom of the tropic acid moiety. In this paper, the results of a comparative study on the physiological dispositions of scopolamine and anisodine, both labeled with ³H by the Wilzbach technic, are reported.Biological materials were extracted with chloroform at an alkaline pH. The chloroform layer was separated and washed with phosphate buffer of pH 8. An aliquet of the extract was transferred to a counting vial and evaporated to dryness. After addition of 5 ml of scientillation liquid (toluene containing ppo 0.5%, popop 0.03% or dioxane containing ppo 0.4%, popop 0.002%, naphthalene 6%) the samples were counted in a scientillation counter (Model F3-353, Hsi-an). The measured radioactivity was shown to be unchanged ³H-scopolamine or ³H-anisodine by specificity tests using thin layer chromatography.Both ³H-scopolamine and ³H-anisodine were found to be well absorbed from rat intestine in situ, but it seemed that ³H-scopolamine was absorbed more rapidly and more completely than ³H-anisodine. After a single intravenous injection of ³H-scopolamine or ³H-anisodine, a plot of the logarithm of drug concentration in plasma versus time yielded a curve with two distinct linear components. For ³H-scopolamine and ³H-anisodine, the T1/2 α were found to be 11 and 13 minutes, and the T1/2β were 95 and 70 minutes, respectively. When given intravenously, the highest levels of ³H-scopolamine and ³H-anisodine were found in the lungs and kidneys respectively. The content of both drugs in the brain was higher than that in the plasma. The distribution patterns of the two drugs over the various regions of the brain were similar: highest levels were found in the striatum, cerebral cortex and hippocampus, moderate levels were found in the septum and diencephalon, and very low levels were obtained in the lower brain stem and cerebellum. The contents of ³H-scopolamine in the brain sections were signi-Ficantly higher than those of ³H-anisodine, although their contents in plasma were similar.Following an intravenous dose of ³H-scopolamine and ³H-anisodine, the total radioactivity excreted in urine was 62% and 78% respectively within 48 hours, while those excreted in feces was 25% and 12.5% respectively. In rats with a biliary cannula, 40% and 20% respectively of an intravenous dose of ³H-scopolamine and ³H-anisodine could be recovered from the bile collected within 48 hours. In the urine, feces or bile, about 1/7 to 1/4 of the excreted total radioactivity was shown to be unchanged drug.³H-scopolamine and ³H-anisodine were shown to be metabolized by rat liver as well as by plasma. ³H-anisodine was shown to be also metabolized by rat kidney slices. Both drugs were rapidly metabolized by liver, kidney and plasma of the rabbit. In this animal, it seemed that the metabolism of ³H-scopolamine was more rapid than that of ³H-anisodine.