Posted by psychobot5000 on November 14, 2006, at 17:05:20
In reply to NEED ADVICE...How to choose a MAO????????, posted by stargazer on November 11, 2006, at 8:14:14
Hi. I read that someone was wondering about the difference between the different MAOis and how they worked, so here's my attempt to sketch out the basics. Hope it's helpful.
____
MAO (MonoAmineOxidase) is a type of enzyme that metabolize/break down neurochemicals, by oxidizing them. The chemicals they break down are (mostly) serotonin, norepinephrine, and dopamine. All of these are thought to be important in depression, as well as other important brain function. The MAO inhibitors block the enzyme, preventing it from destroying these chemicals, and so creating higher levels all throughout the body.There are indeed two kinds of monoamine-oxidase: MAO-A and MAO-B. MAO-A breaks down serotonin and norepinephrine, while MAO-B breaks down dopamine--this is the main difference between the two. It is hard to summarize what each of these chemicals is used for because the subject is so damnably complicated, but broadly speaking, serotonin is thought to be involved in mood, anxiety, digestion, sleep, and other things. Norepinephrine/Noradrenaline (same thing) is involved in drive, wakefulness, heartrate, and much else. Dopamine is involved in memory, learning, movement, drive/motivation, pleasure...the list goes on.
The first antidepressants were unselective MAO inhibitors, meaning that they block BOTH MAO-A and MAO-B. (Nardil, Parnate and Marplan are all of this type) MAO is responsible for breaking down the chemical tyramie that is found in some foods, and causes dangerously increased heartrate and bloodpressure. Anyway, as long as a certain amount of -either- MAO-A or MAO-B is there, unblocked, in the gut, tyramine is prevented from flooding your system. Thus, moclobemide, a selective MAO-A inhibitor, which leaves MAO-b alone, is safe without dietary restrictions, and EMSAM, which prefers MAO-B greatly, is also safe in moderate doses. In either case (unless they are taken together), one half of the MAO is still available to keep your system safe.
So there are three main types of MAO inhibitors:
1) The old, powerful inhibitors of MAO A and B, Nardil, Parnate, and Marplan. Perhaps because of their dual action, these are the most powerful chemical antidepressants medicine has. They are also dangerous because of tyramine, of course.
2)Inhibitors of MAO-A--Moclobemide (not used in the United States) and others. Among the least powerful antidepressants, the focus on MAO-A means they would elevate levels of serotonin and noradrenaline only. This makes them similar to other antidepressants like tricyclics, though tricyclics affect these chemicals with a different mechanism.
3) Inhibitors of MAO-B--Like Selegiline EMSAM. They affect primarily MAO-B and thus, increase dopamine. When taken through the patch, EMSAM doesn't pass directly through the digestive system, and thus has less effect on digestive MAO. The 6mg dose is safe from tyramine interactions. The 9mg and 12mg MAY BE safe as well, however, not enough research has been conducted at that dose, so we don't know.
Another MAO-B inhibitor is Azilect/Rasagiline, which is cleared in the US for parkinson's disease. It has been little-studied in depression, but could (possibly) be as effective as selegiline, if used in high enough doses.
Each individual drug is different. For example, both Parnate/Tranylcypromine and Selegiline/EMSAM metabolise into amphetamine, giving them, and Parnate particularly, more of a peppy feeling, and maybe causing more insomnia. EMSAM has much less of this than oral selegiline, because it goes straight into the blood without being processed by the liver first, as oral is. Selegiline is also a dopamine reuptake-inhibitor, giving it some further impact on dopamine. Some posters on this site believe EMSAM from the patch is more energizing than the oral form, probably because there is a higher ratio of the original substance to the other stuff produced when it passes through the liver from the intestine.
Remember that Parnate is an unselective MAOi, and in fact is clearly the most dangerous in terms of hypertensive crises. Maybe this is because of the modest stimulant effect that automatically goes with it.
Nardil/Phenelzine is unselective (meaning it is not choosy about MAO-A or B) drug that is thought by some to be slightly more powerful than the others. It is especially useful in anxiety, possibly because it also increases levels of GABA in the brain. GABA is an 'inhibiting' neurochemical, the same chemical that diazepam, xanax, and the many other drugs effect. Phenelzine/Nardil is probably also better for sleep than Parnate. Marplan is similar to Phenelzine. It may be less powerful, and have less effect on GABA, but also fewer side-effects. Both of these can be damaging to the liver, though, so one needs to have blood-checks of liver enzymes while taking them.
As far as I know, the theories about deprenyl(selegiline) and phenylethylamine in depression are largely unsubstantiated in terms of hard evidence, but selegiline does indeed increase phenylethylamine levels a great deal, by preventing its breakdown. Because EMSAM/selegiline/deprenyl effects dopamine, as well as these other such chemicals, it COULD be more useful for depressive states with cognitive difficulty than the other MAOis--or at least it might help this stuff just as much with fewer side-effects.
I hope this helps explain some stuff,
P-bot
poster:psychobot5000
thread:702513
URL: http://www.dr-bob.org/babble/20061110/msgs/703458.html