Don't apollo-gise (sorry couldn't resist
). It's these sort of questions for which I eagerly wait and hope for.
Let's see. I realise you know some of this already, but to give as clearer picture as possible..
MAOB is an enzyme. It is relatively selective in regards to what substrates it binds with. It's major role is the breakdown of NA (noradrenaline) and DA (dopamine). MAOB is located throughout the body, where-ever DA or adrenoreceptors are located.
A non-reversible inhibitor is, as you worked out, a molecule which binds to the enzyme and effectively disables it. The enzyme will be broken down and recycled by first being chopped up into smaller proteins which may be reassembled by mRNA prompted enzymes (many). Smaller protein polypeptides cannot form stable secondary structures (the alpha-helix) so can be very prone to being picked up by passing molecules such as enzymes with the "right fit". Sometimes the steric hindrance of smaller protein pieces will result in the assembly of the enzyme from scratch. It is all based upon kinetics, the easiest route always being 1st choice.
When deprenyl binds to MAOB it causes a build up of the endogenous chemicals the enzyme would normally regulate. The normal body's response to increased levels is to release more MAOB or other oxidative enzymes in effort to maintain homeostasis. With a drug like amphetamine this response is far greater than for a drug like deprenyl, because amphetamine causes three basic primary actions, which signals a far greater need for a quick re-adjustment;
Amphetamine works on 3 areas of NA release
Enters the nerve terminal via nor-adrenaline carrier molecule (transporter) via uptake 1 receptors. Here it enters the vesicle via another transporter where it then exchanges itself for normally accumulated NA which is released. MAOB destroys some, but some NA escapes into the synapse. As this happens, more amphetamine enters the terminal (presynaptic axon face) to replace the released NA, thereby continuing the cycle.
Amphetamine also reduces post synaptic receptor uptake with the result being that the actions of NA are also increased.
Amphetamine also inhibits MAOB (slightly)
The action on DA cells is more a secondary action from the above, as with the even smaller affect on 5HT, although no doubt some dopamine is stimulated directly, especially with larger doses.
So amphetamine not only blocks the reuptake, but also stimulates NA release and prevents its breakdown. No wonder it's overall action is so powerful. In contrast, selegiline only works by reducing metabolism via MAOB. The body has other enzymes for this but MAOB is usually the most efficient [?] as a quick on the draw, mopping up soldier. Problem is, as we know MAO oxidation is done via a free radical mechanism....
In contrast deprenyl seems to primarily affect DA uptake in the brain, although the metabolites are the same as L-amphetamine and would be expected to be active to some degree as are the amphetamine metabolites.
An awful part about aging is the apparent role MAOB plays in increasing neural decline. As we age more MAOB is found in the brain, and being the heavy handed hammer it is, free radicals are produced which damage cells. So it is reasoned by many that by reducing levels of MAOB (safely of course) then less neurodegeneration should occur. It is known that deprenyl also enables DA to work more efficiently as has been shown with some late stage parkinsons patients who no longer respond to L-DOPA alone. It seems as though the body's response to L-DOPA is to get rid of it quicker by making more MAOB. This is not the full picture by a long way, but it serves to illustrate why and how deprenyl works.
Enzyme specific drugs designed to bind with MAOB would not be expected to bind with the receptor, and if by chance they did, they would be very unlikely to cause any similar affect. Receptors, like enzymes are amazingly complex molecules. While a drug may fit with several endogenous chemicals; enzymes, receptors, transporters, ion channels etc, it will not cause the same result as the actions of each is so different.
[Correction: The physiological result of binding will be different but either could result in the same outcome e.g. Something which is both a strong inhibitor of MAO-A and stimulates 5HT release could result in high levels of serotonin, producing serotonin syndrome] The actions of some toxins or drugs at a high level is somewhat different, in that cellular death occurs due to severe disruptions in normal function, usually involving a cascading effect.
Do all neurotransmitters work on the axon/electrical signal/axon terminal/synapse/receptors on dendrite wall model that 5-HT does?
No. There are many neurotransmitters, some of which work on ion channels (GABA), some bind to G protein receptors (5HT), some work on Kinase(enzyme)-linked receptors in cell walls, resulting in many cellular effects. Others operate on gene transcription receptors within the nucleus of the cell. During the journey to its target receptor, a molecule may be shuffled, piggybacked or chemically altered before it crosses the cell membrane where it is converted back to its original form.
NO or nitric oxide is an example of a neurotransmitter which binds to enormous numbers of bio-molecules. It was only discovered to be a neurotransmitter some 20 years ago, and not until the last few years that it's roles have been deduced. There is still much to learn about NO, including it's role in apoptosis (programmed cell death)
OK, I don't actually own a neuroscience text, although I understand there are some goods ones. The forbidden site reviewed one around a year ago. It looked great but was too much for me to spend.
I suggest getting a really good anatomy and physiology text, a good pharmacology text, and the best biochemistry text. IMHO you should also get a good organic text. All this adds up to a lot of money, so start with the anatomy/physiology. Martini is an excellent text, comes with online support and applications manual. The neurology and nervous system sections are very comprehensive with a well detailed text. I do have many good neuro papers if you're interested.
Cheers, you know what to do if you need any details.
