IDEAS CONCERNING THE RELEASE OF NITRIC-OX IDE 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 wit h the theoretical background of the literature. Then a system with low molecular tetraphenylporphrin complexes (TPP), with the transition me tals iron and manganese as central ions instead of the iron chelate in cytochrome P-450, was established. We use NaBH4 as a reducing agent i n these cases. In the detection of nitric oxide we succeeded with a ch emiluminescence method using ozone to activate nitric oxide. Under the se 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 o f nitric oxide was only observed in the case of SNAP, while SNP, nitri te, and GTN are stable in the dark under anaerobic or aerobic conditio ns. If these compounds are activated under reductive conditions with ( FeTPP)-T-II or by illumination with visible light, we measure NO-relea se in all cases. Particularly remarkable is the enhancement of the NO- release when these two activation methods are combined. With these exp eriments the activation mechanism of NO-containing compounds is discus sed, and an enzymatic pathway involving the reductive site of cytochro me P-450 seems to be possible.