[Spectral changes in the liver microsomal cytochrome P-450 of rats during interaction with phenazepam and its...

Phenazepam (I) and 3-hydroxymetabolite (II) interacting with cytochrome P-450 of the liver of rats administered phenobarbital and 3-methylcholantrene demonstrated the 2nd type of spectral changes in hemoprotein. The binding constants of I and II considerably differ, which points to the possibility of interaction of substrates with different areas of hemoproteins. The characteristic points (maximum, minimum, isobestic) of the cytochrome P-450 spectrum were displaced during II titration to the longwave region as compared with I. The calculation of electron density on the atoms of the heterocycle and aromatic nuclei of the molecules of I and II has shown that the differences in the spectra of I and II binding with cytochrome P-450 are determined by the distribution of electron density of their heterocycle.