A COMPARATIVE AUTORADIOGRAPHIC STUDY ON DISTRIBUTION OF DEPTROPINE CITRATE AND DEPTROPINE METHIODIDE IN MICE

The distribution patterns of deptropine citrate-N-14CH3 and deptropine methiodide-N-14CH3 were studied in female mice by means of a macroautoradio-graphic technique. The distribution of deptropine, both after oral and intraperitoneal administration shows a number of aspects which seem to be common for a group of structurally related basic drugs: a large volume of distribution of the radioactivity with highest levels in glandular tissue, lungs, lymphoid tissue, bone marrow, bile and specified zones in kidney and adrenals. The concentration of radioactivity in the brown fat and the high and prolonged level of radioactivity in the liver are related to N-demethylation and/or hydrolysis of deptropine-N-14CH3. Compared with structurally related compounds studied earlier the deptropine radioactivity penetrates into the brain only to a small extent; remarkable are concentrations in the choroid plexus of the lateral and fourth ventricles, and sometimes in the walls of the former. Quaternisation of the deptropine molecule, as in deptropine methiodide, leads to important changes in the distribution pattern of the radioactivity. After oral administration of deptropine methiodide-N-14CH3 the radioactive material is very effectively restricted to the gastrointestinal tract; most of the absorbed amount is cleared from the circulation by the liver and brought back into the intestinal tract via the bile. After i.p. administration, the shorter intervals showed not only a large amount of radio-activity in the peritoneal cavity but also in the thoracic cavity. Outside these cavities the salivary glands and thyroid gland show some accumulation of radioactivity. Bile, intestinal contents and especially the peritoneum show a long retention of the radio-activity. © 1969.