Posted by King Vultan on October 5, 2004, at 12:30:40
In reply to Difference between MAO-A and MAO-B? which drugs?, posted by ravenstorm on October 5, 2004, at 11:17:52
Parnate, Nardil, and Marplan are all irreversible, nonselective MAO inhibitors. That means that when they bind to either MAO-A or MAO-B, that particular MAO molecule is rendered forever useless. This is in contrast to both moclobemide and selegiline. Moclobemide is a selective, reversible inhibitor of only MAO-A. It does not affect MAO-B at all (because it's selective) and also has the ability to undock from the MAO-A molecule in certain situations (because it's reversible).
Selegiline at low doses is a selective, irreversible inhibitor of MAO-B. That means it ignores MAO-A and binds only to MAO-B, which it also renders permanently useless as Nardil also does, for instance, because selegiline is an irreversible inhibitor of MAO-B. At higher dosages, selegiline loses its selectivity and starts binding to MAO-A irreversibly along with MAO-B, becoming the same in that respect as Nardil, Marplan, and Parnate.
As far as the implications of all this, MAO-A has the ability to metabolize serotonin, norepinephrine, and dopamine, but it is the first two that it seems to be more linked to in actual practice, and serotonin and norepinephrine are the problematic neurotransmitters as far as causing the reactions you can get on an MAOI if you eat the wrong thing or take the wrong drug. MAO-B seems to be more associated with dopamine, which is not as problematic. So selegiline really has no effect on serotonin and norepinephrine levels at lower dosages, so no dietary restrictions are required. At higher dosages, selegiline begins to also permanently disable MAO-A, which increases the availability of serotonin and norepinephrine and necessitates the implementation of the dietary restrictions.
Moclobemide shouldn't require dietary restrictions even though it affects MAO-A because it does not bind to the MAO permanently and can detach when necessary and allow the MAO to perform its normal function. The implication also is that its antidepressant effect may not be as robust as the irreversible, nonselective MAOIs because it may detach in the presence of serotonin or norepinephrine and allow these neurotransmitters to be gobbled up by the MAO-A. This is the exact opposite of what an MAO inhibitor is supposed to do.
The older nonselective, irreversible MAOIs basically inhibit both MAO-A and MAO-B at all dosages and cannot detach under any circumstances. I've seen Parnate referred to as "reversible" or "partially reversible" in some references, but I don't know exactly what they're talking about or how true that is. Studies have shown that Parnate definitely has the most ability of any of the MAOIs to cause a hypertensive crisis while under treatment. However, after cessation of treatment, the MAO-A activity for Nardil does take a much longer time to return to normal than it does for Parnate.
Todd
poster:King Vultan
thread:399167
URL: http://www.dr-bob.org/babble/20041002/msgs/399207.html