The novel
MAO-B inhibitor
PF9601N, its
cytochrome P450-dependent metabolite FA72 and
l-deprenyl were studied as potential
peroxynitrite (ONOO(-)) scavengers and
nitric oxide synthase (NOS) inhibitors. The scavenging activity of these compounds was evaluated by measuring the oxygen consumption through
peroxynitrite-mediated oxidation of both
linoleic acid and brain homogenate. FA72,
PF9601N and
l-deprenyl caused a concentration-dependent inhibition of ONOO(-)-induced
linoleic acid oxidation with an IC(50) value of 60.2 microM, 82.8 microM and 235.8 microM, respectively. FA72 was the most potent also in inhibiting ONOO(-)-induced brain homogenate oxidation with an IC(50) value of 99.4 microM, while
PF9601N and
l-deprenyl resulted weaker inhibitors in the same experimental model, showing an IC(50) value of 164.8 and 112.0 microM, respectively. Furthermore, both the novel
MAO-B inhibitor as well as its metabolite were able to strongly inhibit rat brain neuronal NOS (IC(50) of 183 microM and 192 microM, respectively), while
l-deprenyl at the highest concentration used (3 mM), caused only a slight decrease of the
enzyme activity. Moreover, inducible NOS was strongly inhibited by FA72 only. All these results suggest that
PF9601N could be a promising therapeutic agent in
neurodegenerative disorders such as
Parkinson's disease.