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

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 binding in 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. Both in vitro and in 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.