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Uptake and excretion of the quaternary ammonium compound deptropine methiodide in the isolated perfused rat liver

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Summary

The metabolism of 3α-[(10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5-yl)oxy]-8-methyltropanium iodide (deptropine methiodide; N-methyldeptropine), a potential agent for the treatment of peptic ulcers and gastrointestinal spasms, was studied by passing the N-14CH3-labelled compound through the isolated perfused rat liver. The substance was rapidly taken up by the liver. This process followed first-order kinetics with a half-life of 5 min. It was calculated that 94% of the drug was removed by the liver during one passage. About 70% of the initial radioactivity was excreted in the bile during a perfusion period of 2 h. This elimination process exhibited first-order kinetics with a half-life of about 25 min.

N-Methyldeptropine was found to be broken down in the liver into N-methyltropine, and a non radioactive fragment. N-methyltropine and N-methyldeptropine were eliminated in the bile. The former also diffused back into the perfusion fluid. In addition, the bile contained an uncharacterised radioactive product related to N-methyltropine, possibly a complex of N-methyltropine with bile components.

Both the rapid uptake of N-methyldeptropine in the liver and the biotransformation into products with a much lower pharmacological and toxicological potency, should lessen the likelihood of side effects outside the gastrointestinal tract after oral dosage.

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Authors and Affiliations

  1. Gist-Brocades N.V. Research & Development, Haarlem, Netherlands

    U. I. Lavy & W. Hespe

  2. Department of Pharmacology, University of Groningen, Groningen, Netherlands

    D. K. F. Meijer

Authors
  1. U. I. Lavy
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  2. W. Hespe
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  3. D. K. F. Meijer
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Additional information

Deptropine methiodide will be referred to as MDT.

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Lavy, U.I., Hespe, W. & Meijer, D.K.F. Uptake and excretion of the quaternary ammonium compound deptropine methiodide in the isolated perfused rat liver. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 183–192 (1972). https://doi.org/10.1007/BF00508906

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  • DOI: https://doi.org/10.1007/BF00508906

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