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Re: Mode of action unknown / MAO Chairman_MAO

Posted by Larry Hoover on May 9, 2005, at 9:59:45

In reply to Re: Mode of action unknown / MAO Larry Hoover, posted by Chairman_MAO on May 8, 2005, at 18:56:54

> > I believe MAO is a synaptic cleft enzyme, designed to "corral" any stray neurotransmitter that didn't: a) hit its designated receptor (post-synaptic); b) hit its designated auto-receptor (pre-synaptic); c) get vacuumed up by the reuptake pump (pre-synaptic). Inhibiting MAO would, presumably, slightly enhance all of the above. However, it shunts "escaped" neurotransmitters to other scavenger enzymes, e.g. COMT. Thus, the metabolites of the catecholamines must change proportion and concentration. Perhaps that is the mode of action, metabolite-mediated response elements.
> >
> > Lar
> Note how MAO-A is found intraneuronally as well. Thus MAOIs alter the amount of neurotransmitter available for release. One possible therapeutic mechanism I can postulate a priori is that certain people have disorders that perturb the storage of neurotransmitters inside neurons. MAOIs could allow proper amounts of the transmitter to accumulate. I don't know if this has ever been discussed in the literature or not--or if it even makes total sense, heh--just came to mind.

Thanks for expanding my knowledge. I just checked my mid-90's textbooks, and there is no mention of intraneuronal MAO.....only iterneuronal.

Note, in the diagram, though.....COMT is also intraneuronal. When you have two concurrent but divergent paths, and you inhibit one, you shunt to the other. I still think the COMT metabolites go on to trigger response elements, which lead to transduction via DNA/RNA/protein synthesis....i.e. gene regulation.

> Contrarily, while MAO-A is found in synapses as well as intraneuronally in catacholaminergic neurons, MAO-B is primarily a glial enzyme and is also found in serotonergic neurons.

Yes, that is now considered to be the primary active site of e.g. selegiline....the glia. We still don't know much about what the glia do. A decade ago, they were thought of as support cells, ones without regulatory activity. We now know that they are primary regulatory sites, initiating cascades of modulatory action.

Although fascinating to ponder, I must return to my critical thinking the end, this is all what my favourite professor used to call hand-waving. "I know! I know!" <hands waving in the air>

We don't know, unfortunately.





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