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.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000097:blood*; D001569:Benzodiazepines / Q000097:blood*; D001798:Blood Proteins / Q000378:metabolism* / Q000528:radiation effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003975:Diazepam / Q000494:pharmacology* / Q000652:urine; D005243:Feces / Q000032:analysis; D008297:Male; D010777:Photochemistry; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D001569:Benzodiazepines; D003975:Diazepam