Untersuchungen zum Stoffwechsel von Tropan-Alkaloiden, VI. Chemische Analyse des Stoffwechsels von Atropin bei der Maus

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Abstract
The metabolism of atropine by the mouse was studied with the aid of atropine labelled in 3 different ways (9-14C; 8[image]-14C; 3H-polytope). The alkaloid disappeared from the blood in the 1st 1/2 hr. after intravenous injection, and at the same time showed a marked accumulation in the liver, spleen and small intestine. In the 2nd 1/2 hr. after injection, the radioactivity in the liver decreased, while the activity in the blood increased again. This finding can be explained by a brief binding of atropine by the liver, followed by release of metabolites into the blood. There is no appreciable longer term incorporation of atropine or its metabolites into the body constituents. The organs with highest radioactivity were kidney, liver, intestine and lungs. The lowest activity was found in the brain. After 3 hr., the total excretion was 60% of the injected activity; after 60 hr. it was 95%. The expired 14CO2 is derived from the N-CH3 group of the alkaloid. After the injection of atropine labelled in the tropic acid, there was no detectable radioactivity in the expired air. From the distribution of activity in the intestine, it was concluded that atropine and its metabolites pass from the liver via the bile into the intestine where they are partially resorbed. Radioactive substances are excreted from the blood into the intestine; an entero-hepatic circulation is established, so that the removal of the alkaloid and its metabolites from the body is delayed. From the chemical characterisation of the atropine metabolites, the following metabolic reactions of the atropine molecule in the mouse were established: The aliphatic side chain of the tropic acid residue in the atropine becomes conjugated with glucuronic acid. The atropine is hydroxylated at position 4[image] (in the benzene ring of the tropic acid residue), followed by conjugation with glucuronic acid. The ester linkage between tropine and tropic acid is hydrolyzed. The nor-derivative of atropine, and presumably of some of its derivatives, is formed by oxidation of the N-methyl group to CO2, which is expired. Only glucuronides of atropine or its derivatives were found in the bile.

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