IDEAS CONCERNING THE RELEASE OF NITRIC-OXIDE FROM NO-CONTAINING DRUGS - MODEL REACTIONS IN THE PRESENCE OF LIGHT AND METAL-COMPLEXES

The metabolism of NO-containing compounds was imitated with reductive model reactions for cytochrome P-450. First this model is compared with the theoretical background of the literature. Then a system with low molecular tetraphenylporphrin complexes (TPP), with the transition metals iron and manganese as central ions instead of the iron chelate in cytochrome P-450, was established. We use NaBH4 as a reducing agent in these cases. In the detection of nitric oxide we succeeded with a chemiluminescence method using ozone to activate nitric oxide. Under these conditions different NO-containing drugs, e.g. sodium nitroprusside (SNP), inorganic nitrite, glycerol trinitrate (GTN), and S-nitroso-N-acetyl-penicillamine (SNAP), are investigated. A spontaneous release of nitric oxide was only observed in the case of SNAP, while SNP, nitrite, and GTN are stable in the dark under anaerobic or aerobic conditions. If these compounds are activated under reductive conditions with (FeTPP)-T-II or by illumination with visible light, we measure NO-release in all cases. Particularly remarkable is the enhancement of the NO-release when these two activation methods are combined. With these experiments the activation mechanism of NO-containing compounds is discussed, and an enzymatic pathway involving the reductive site of cytochrome P-450 seems to be possible.