Pharmaceutisch Weekblad

, Volume 5, Issue 6, pp 302–307 | Cite as

Correlations between phototoxicity of some 7-chloro-I,4-benzodiazepines and their (photo)chemical properties

  • H. De Vries
  • G. M. J. Beijersbergen Van Henegouwen
  • P. J. H. H. Wouters
Original Articles


In relation to the phototoxicity of 7-chloro-1,4-benzodiazepine-N-oxides the photostability of some of theseN-oxides and the thermostability of their photoproducts, the oxaziridines, were studied. Rather than a consequence of a direct phototoxic effect by theN-oxides the ultimate toxic effect in the test systemSalmonella typhimurium appeared to be caused by products formed during and after the irradiation. For chlordiazepoxide (Cdz) and its main metabolites in man desmethylchlordiazepoxide (Des) and demoxepam (Dem) the formation of an oxaziridine is indeed a crucial factor for the onset of the toxic effect. However,Dem oxaziridine (Dem Ox.) being very thermolabile in protic medium forms non-toxic conjugates with the solvent,Cdz Ox. andDes Ox. are thermally converted into theirN-oxide, althoughDes Ox. partly decomposes into 6-chloro-4-phenylquinazoline-2-carboxaldehyde as well. This compound proved to be an important factor in the toxic action ofDes after irradiation.


Public Health Internal Medicine Toxic Effect Chemical Property Chlordiazepoxide 
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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1983

Authors and Affiliations

  • H. De Vries
    • 1
  • G. M. J. Beijersbergen Van Henegouwen
    • 1
  • P. J. H. H. Wouters
    • 1
  1. 1.Department of Pharmacochemistry, Subfaculty of PharmacyState University of Leiden, Gorlaeus LaboratoriesRA LeidenThe Netherlands

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