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European Journal of Clinical Pharmacology

, Volume 20, Issue 3, pp 219–224 | Cite as

Antifolate effect of triamterene on human leucocytes and on a human lymphoma cell line

  • A. Schalhorn
  • W. Siegert
  • H. -J. Sauer
Originals

Summary

The inhibitory effect of triamterene and its metabolites on human leucocyte dihydrofolate reductase has been studied. Under test conditions with dihydrofolic acid 0.5×10−5 M, triamterene 7×10−5 M produced total enzyme inhibition, whereas the metabolites hydroxytriamterene and the sulphate ester of hydroxytriamterene were less effective inhibitors; at their maximum attainable concentration of 5×10−5 M, dihydrofolate reductase was inhibited by 80% and 50%, respectively. Cultures of the BJAB-B95-8 human lymphoma cell line were incubated with various concentrations of triamterene. Because of their increased specific activity of dihydrofolate reductase, the cells were able to maintain normal DNA metabolism, as measured by the ratio of the incorporation rates of 3H-deoxyuridine and 3H-thymidine, as well as normal cell growth at 1×10−6 M, and in some cases at 1 × 10−5 M triamterene. At 8×10−5 M triamterene, the strong inhibitory effect caused severe impairment of DNA metabolism and subsequently dissolution of the cell culture. The results are discussed in relation to the possible toxic side effects of long-term triamterene treatment in patients suffering from alcoholic cirrhosis, who may have impaired metabolism of triamterene and a concomitant severe folate deficiency.

Key words

triamterene folate antagonism triamterene metabolites dihydrofolate reductase DNA metabolism human leucocytes BJAB-B95-8 lymphoma cell line 

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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • A. Schalhorn
    • 1
  • W. Siegert
    • 1
  • H. -J. Sauer
    • 1
    • 2
  1. 1.Medizinische Klinik IIIKlinikum Großhadern der Ludwig-Maximilians-Universität MünchenMünchenFederal Republic of Germany
  2. 2.Department of Clinical HaemotologyInstitute of Haematology of the Gesellschaft für Strahlen- und Umweltforschung mbHMünchenFederal Republic of Germany

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