Pyridazinone derivatives have considerable kinds of biological activities such as those cardiotonic,platelet aggregation inhibitory,anti-inflammatory,aldose reductase inhibitory,antifungal and so on.
This is probably one of the number one reasons when you look at the different conditions, health conditions, comorbidities, when people don't respond to PDF5 inhibitors.
Nitric oxide is kind of difficult too, because a lot of things that decrease it, if you take it long enough, your body will become better at making it and actually make less phosphodiesterase enzymes.