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Pharmaceutisch Weekblad

, Volume 10, Issue 3, pp 122–129 | Cite as

Photobinding of some 7-chloro-1,4-benzodiazepines to human plasma protein in vitro and photopharmacology of diazepam in the rat

  • A. Bakri
  • G. M. J. Beijersbergen Van Henegouwen
  • H. De Vries
Original Articles

Abstract

The extent to which diazepam, diazepam-N4-oxide and N4-desoxychlordiazepoxide irreversibly bind to plasma protein upon UV irradiation was determined. Comparison with the results for chlordiazepoxide leads to the conclusion that the N4-oxide function is essential for the occurrence of irreversible bindingin vitro. Investigation of the photopharmacology of diazepam in the rat gave results similar to those for N4-desoxychlordiazepoxide: in contrast with what already had been found for chlordiazepoxide no difference was observed between the pharmacology of diazepam in UV-A irradiated rats and those kept in the dark. Bothin vitro andin vivo data expand the hypothesis to other 7-chloro-1,4-benzodiazepines, according to which the presence of an N4-oxide group is a prerequisite for the occurrence of phototoxicity and that an oxaziridine is the toxic intermediate.

Keywords

7-Chloro-1,4-benzodiazepines Diazepam Metabolism Phototoxicity Protein binding 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1988

Authors and Affiliations

  • A. Bakri
    • 1
  • G. M. J. Beijersbergen Van Henegouwen
    • 1
  • H. De Vries
    • 1
  1. 1.Center for Bio-Pharmaceutical Sciences, Division of Medicinal ChemistryState University of LeidenRA Leidenthe Netherlands

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