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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Questionmark on March 13, 2006, at 0:32:51
This is more for just curiosity/knowledge's sake than practical value right now, but...
The abstract below states the following:"A single dose of deprenyl had no significant effect on striatal efflux of DA. The results show that DA metabolism was reduced only by clorgyline [[an MAO-A inhibitor]], whereas neuronal release of DA was enhanced by both MAO-A and MAO-B inhibitors on chronic administration. The enhanced DA release by chronic MAO-B inhibition does not appear to be dependent on production of amphetamine-like metabolites of the inhibitor. Possible mechanisms for the release-enhancing effect of the MAO-B inhibitors include elevation in levels of endogenous beta-phenylethylamine, or an inhibition of DA reuptake, which develops only on chronic administration, because both deprenyl and TVP-1012 have only very weak effects on amine uptake in acute experiments."
Does this suggest that MAO-A is more responsible for breakdown of dopamine than MAO-B?
Because, it appears these results suggest that inhibition of *MAO-A* results in a direct increase in dopamine levels more than inhibition of *MAO-B* does (as a *direct* result of the MAO-B inhibition)....
and that the reason MAO-B inhibitors show such a dramatic increase in dopamine transmission is due to their action of increasing phenylethylamine levels (which i gather is a result of increased conversion of the amino acid phenylalanine to phenylethylamine by MAO-B?)-- and possibly to some extent, DA reuptake inhibition, i guess.Is this right or am i missing something here?
If this IS right, then couldn't taking anything that significantly increases phenylethylamine levels-- such as "chocamine"-- be roughly as effective at promoting DA transmission as selegeline (at least low-dose selegeline)??
Thoughts?Effect of long-term treatment with selective monoamine oxidase A and B inhibitors on dopamine release from rat striatum in vivo.
Lamensdorf I, Youdim MB, Finberg JP.
Journal of Neurochemistry, 1996 Oct; 67(4):1532-9.ABSTRACT
Acute inhibition of monoamine oxidase B (MAO-B) in the rat does not affect striatal dopamine (DA) metabolism, but chronic MAO-B inhibition with deprenyl has been reported to increase the release of striatal DA, as shown using in vitro techniques. To see whether chronic MAO-B inhibition also causes an increase in DA release in vivo, rats were treated for 21 days with either deprenyl (0.25 mg/kg), TVP-1012 [R(+)-N-propargyl-1-aminoindan mesylate; 0.05 mg/kg], an irreversible inhibitor of MAO-B that is not metabolized to amphetamines, clorgyline (0.2 mg/kg), or saline (all doses once daily by subcutaneous injection). Concentric 4-mm-long microdialysis probes were implanted in the left striatum under pentobarbital/chloral hydrate anesthesia on day 21, and microdialysate DA, 3,4, dihydroxyacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenyl acetic acid (HVA) were determined in the conscious animals on day 22. Baseline levels of DA were as follows: control, 0.34 +/- 0.04 (n = 13); deprenyl, 0.88 +/- 0.10 (n = 8, p < 0.01); TVP-1012, 0.94 +/- 0.20 (n = 7, p < 0.01); clorgyline, 0.90 +/- 0.12 (n = 7, p < 0.01) pmol/20 min. Levels of DOPAC and HVA were reduced only in the clorgyline-treated group. The incremental release of DA induced by depolarizing concentration of K+ (100 mM bolus of KCl in perfusate) was significantly greater in clorgyline- and deprenyl-treated rats and elevated (nonsignificantly) in TVP-1012-treated rats. Chronic treatment with the MAO-B inhibitors reduced striatal MAO-B activity by 90%, with 15% (TVP-1012) or 40% (deprenyl) inhibition of MAO-A. Clorgyline inhibited MAO-A by 95%, with 30% inhibition of MAO-B. A single dose of deprenyl (0.25 mg/kg, 24 h before microdialysis) had no significant effect on striatal efflux of DA. The results show that DA metabolism was reduced only by clorgyline, whereas neuronal release of DA was enhanced by both MAO-A and MAO-B inhibitors on chronic administration. The enhanced DA release by chronic MAO-B inhibition does not appear to be dependent on production of amphetamine-like metabolites of the inhibitor. Possible mechanisms for the release-enhancing effect of the MAO-B inhibitors include elevation in levels of endogenous beta-phenylethylamine, or an inhibition of DA reuptake, which develops only on chronic administration, because both deprenyl and TVP-1012 have only very weak effects on amine uptake in acute experiments.
Posted by gibber on March 13, 2006, at 21:22:33
In reply to Abstract-- (MAO-A vs. MAO-B, dopamine), posted by Questionmark on March 13, 2006, at 0:32:51
I can't address your question as a whole because I just don't know, but I did want to point out one error in your arguement. Phenylalanine is not converted to phenylethylamine by MAO-B. This must be catalyzed by a different enzyme. MAO-B instead quickly breaks down phenylethylamine, so taking a MAO-B inhibitor will allow PEA to accumulate. Note: I'm taking DLPA and 10mg of selegiline right now and not noticing any strong antidepressive qualities yet.
Posted by willyee on March 14, 2006, at 3:57:48
In reply to Re: Abstract-- (MAO-A vs. MAO-B, dopamine), posted by gibber on March 13, 2006, at 21:22:33
I actualy found liq deprenyl and simple caffiene tablets more effective than the WHOLE dlpa OR sime l - phenlyanine fad.
I know this combo started in smart drugs with the mentioning of the big study,maybe try adding it in,or replacing the dlpa?
Caffiene also has a effect on dopamine im sure,anyway it was working for me.
Posted by Questionmark on March 14, 2006, at 4:30:53
In reply to Re: Abstract-- (MAO-A vs. MAO-B, dopamine), posted by gibber on March 13, 2006, at 21:22:33
> I can't address your question as a whole because I just don't know, but I did want to point out one error in your arguement. Phenylalanine is not converted to phenylethylamine by MAO-B. This must be catalyzed by a different enzyme. MAO-B instead quickly breaks down phenylethylamine, so taking a MAO-B inhibitor will allow PEA to accumulate. Note: I'm taking DLPA and 10mg of selegiline right now and not noticing any strong antidepressive qualities yet.
Yes, i'm glad you pointed that out. I actually realized the error in that shortly after (or maybe the day after) writing & posting it when i read an abstract in which they administered oral phenylethylamine with 10mg (i think) selegeline so that, as it said, it would not be immediately metabolized (is this incorrect to say "metabolized" and not "catalyzed"?) by MAO-B in the body. i was going to go back and write a brief "Correction" post, but i did not get around to it. But that's okay cuz you did basically. So, thank you.
Wait a minute, i have a question. Is phenylethylamine ever present long enough to have effects in the body when MAO-B is not being inhibited? i mean i automatically assume yes but how if it is metabolized so quickly when ingested (or when formed in the body, if it is formed in the body)?By the way, what willyee said in his post is interesting. That could be pretty significant.
i'd really like to get some liquid deprenyl and try it at very low doses for awhile.
Posted by gibber on March 14, 2006, at 10:46:36
In reply to Re: Abstract-- (MAO-A vs. MAO-B, dopamine), posted by Questionmark on March 14, 2006, at 4:30:53
I guess I use catalyze, metatabolize, "break down" interchangably. Bio geeks may take exception to that...I was one in college. THe PEA issue you bring up is curious. So appearently the theory is healthy people may have more PEA. But if PEA is, um, metabolized rapidly regardless of mental health, why would healthy people have more?
Posted by rvanson on March 17, 2006, at 16:33:05
In reply to Re: Abstract-- (MAO-A vs. MAO-B, dopamine), posted by gibber on March 13, 2006, at 21:22:33
> I can't address your question as a whole because I just don't know, but I did want to point out one error in your arguement. Phenylalanine is not converted to phenylethylamine by MAO-B. This must be catalyzed by a different enzyme. MAO-B instead quickly breaks down phenylethylamine, so taking a MAO-B inhibitor will allow PEA to accumulate. Note: I'm taking DLPA and 10mg of selegiline right now and not noticing any strong antidepressive qualities yet.
I have the distinct believe that Emsam will be another flop. I too tried selegiline at higher doses and frankly, it was a waste of time.Check out the drop-out rates in the pre-realese studies of Emsam and I think that one can see that this is a weak drug for major depression.
Having said that, I hope I am mistaken.
Posted by germanium on March 21, 2006, at 3:37:24
In reply to Re: Abstract-- (MAO-A vs. MAO-B, dopamine) EMSAM, posted by rvanson on March 17, 2006, at 16:33:05
Just because a lot of people dropped out doesn't mean that it is a bad antidepressant besides there are many reasons people drop out.
My personal experience with low dose selegiline shows that it works for me very well (2.5 mg).The Depression lifted & I had significantly more energy than without selegiline.
The only side effects that I had was insomnia that subsided in 2 weeks &some short duration tremors
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