Sildenafil is a high-affinity, somehow specific phosphodiesterase type 5 inhibitor. There are 12 different phosphodiesterases in the human body. Phosphodiesterase type 5 is predominant in penile tissues.
In the case of human erections, the method of action, including that of phosphodiesterase inhibitors, is as follows:
If sexual arousal occurs in the brain, nerve terminals in the penis release nitric oxide. The nitric oxide activates the enzyme guanylate cyclase to catalyse GTP (guanosine triphosphate) into cGMP (cyclic guanosine monophosphate). The cGMP acts as second messenger (the first is the nitric oxide) on the smooth muscles in penile blood vessels causing them to dilate. This enlarges the penis by allowing more blood flow into it, and ultimately makes an erection.
The erection is supposed to be temporary. In order to assure that it is temporary, the cGMP must go away. This is effected by the class of enzymes known as phosphodiesterases. They break the diester bonds in cGMP.
In older men, and in those suffering from erectile dysfunction, there isn't enough cGMP to cause an erection, and the little that is there is quickly deactivated by phosphodiesterase. It's like nature doesn't want old men to be sexually active.
When sildenafil is ingested, a high percentage of it binds at phosphodiesterase type 5 in comparatively short time. Thus, many phosphodiesterase molecules are deactivated, and stay deactivated until the sildenafil is cleared. More cGMP is around, and it accumulates. This enlarges the penis for an erection and beyond.
The "beyond" has to be emphasized here. As any routine Viagra user will have noticed, the penis stays enlarged for a few hours after an erection, even though there is no sexual arousal, and no stiffness (because backflow venous valves are open).
Sildenafil is a phosphodiesterase inhibitor with a high affinity. This means that shortly after ingestion (around an hour, if p.o. = per os = oral administration), many sildenafil molecules form a comparatively strong bond with the receptor, in this case phosphodiesterase molecules. This is what high affinity means in pharmacodynamics.
Krachai dam (Kaempferia parviflora) and fingerroot (Boesenbergia rotunda) are low affinity phosphodiesterase inhibitors? When they circulate in penile tissue, they bind to phosphodiesterase, but the bond is not as strong as with sildenafil, and a smaller overall percentage binds to the receptors.
While this sounds like a shortcoming, there are several rationales in using agents of lower affinity.
Because the bonds are not as strong, there is a lower risk of overdosing, as other physiological control mechanisms can kick in.
Furthermore, pharmacologically active ligands (the chemical that bind to a receptors) may have advantages in maintainance dosing. Because lower-affinity pharmacological agents are less likely to spike, they are less disruptive. In opiate addiction, methadone is a low-affinity replacement for morphine and heroine. It binds to opiate receptors, but less dramatically.
These aspects are important to know when considering krachai dam and fingerroot for erectile health and penile enlargement.
The two herbals reduce the effects of phosphodiesterase but more gradually than sildenafil. It's not that yesterday a man couldn't get it up, and today he has an erection.
Rather, these two herbals cause erectile health more subtly. It's like a man will forget that there ever was something wrong with his erections.
Furthermore, low-affinity phosphodiesterase inhibitors are the only sensible option to condition penile tissue to be of a bigger mass (more blood in the sponge at any time).
High-affinity synthetic phosphodiesterase inhibitors are likely to have more side effects because fewer other physiological control mechanisms have a chance.
(Addendum: phosphodiesterase inhibitors also play a role in the prevention of heart disease and dementia.)