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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 ravenstorm on October 5, 2004, at 11:17:52
What is the difference and which MAOI's do what? Do Nardil, parnate and marplan both A and B? What about moclobemide and selegeline?
I thought I read somewhere that parnate doesn't affect dopamine (?) I thought MAOI's affected serotonin, dopamine, norepenephrine.
Clearly, I need some educating on all this. Would someone mind enlightening me?
Thanks in advance to anyone willing to help!
RS
Posted by Hervé on October 5, 2004, at 12:08:32
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 : non selective IMAO (both A and B)
Moclobemide : selective A
Selegiline : Selective BThe on-label usage of selegiline is Parkinson's desease.
Others are antidepressant.
A selegiline patch is in preparation as antidepressant.
Posted by zuzu80 on October 5, 2004, at 12:09:36
In reply to Difference between MAO-A and MAO-B? which drugs?, posted by ravenstorm on October 5, 2004, at 11:17:52
I would think that parnate would also affect dopamine. MAOI (Monoamine Oxidase Inhibitors) work usually unselectively ie they inhibit both MAO-A and MAO-B. MAO-A inhibits the degradation of Serotonin, Noradrenaline and Dopamine in the Central Nervous System (esp in neurons). Parnate as well as Nardil and others would thus affect the 3 neurotransmitters. Selegiline at low doses 5-10mg is selective and affects mainly dopamine (by mainly inhibiting MAO-B) but at higher doses it becomes non selective and affects the three monoamines.
This last point about selegeline has became doubted recently. MAO-B appears to reside mainly in glaial cells rather than neurons, and researchers think that dopamine in the neurons gets degraded by MAO-A. However, me and many others who took it at low doses notice the increased energy and motivation so researchers think that it has a clinical effect even if it only increases dopamine in the glial cells (the cells that support neurons). Selegiline is thought to increase the output potential of catecholamine (NA and DA) neurons since it gets metabolized in the liver to amphetamine and methamphetamine.
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
Posted by ravenstorm on October 5, 2004, at 17:18:28
In reply to Re: Difference between MAO-A and MAO-B? which drugs?, posted by King Vultan on October 5, 2004, at 12:30:40
Thanks for all the information. I think I understand now. BUT, if Nardil, parnate and marplan are all MAO-a and b and affect the same neurotransmitters, why do they affect people so differently? ie, I hear parnate described as activating and nardil described as good for anxiety. What causes the difference? I would think if parnate also affects serotonin then it would be OK for people with anxiety disorders to take it, but perhaps I am wrong.
Thanks everybody, for taking the time to educate me. RS
Posted by Sad Panda on October 5, 2004, at 22:48:41
In reply to Re: Difference between MAO-A and MAO-B? which drugs?, posted by ravenstorm on October 5, 2004, at 17:18:28
> Thanks for all the information. I think I understand now. BUT, if Nardil, parnate and marplan are all MAO-a and b and affect the same neurotransmitters, why do they affect people so differently? ie, I hear parnate described as activating and nardil described as good for anxiety. What causes the difference? I would think if parnate also affects serotonin then it would be OK for people with anxiety disorders to take it, but perhaps I am wrong.
>
> Thanks everybody, for taking the time to educate me. RS
>
>Hi RavenStorm,
The MAOI molecules do 'double duty', primarily, they render MAO usless, secondarily, the molecules have other actions as well, Nardil acts like a benzo, Parnate acts like an amphetamine.
Cheers,
Paul.
Posted by Cruz on October 6, 2004, at 10:24:42
In reply to Re: Difference between MAO-A and MAO-B? which drugs?, posted by ravenstorm on October 5, 2004, at 17:18:28
I wish there was an understanding of how psychatrophic meds work, but there is'nt. About 25 years ago I began to doubt the monoaminergic theories. As time has gone by more and more research has added more doubt to these theories. For any of us to state that a certain med's mode of action is by modifying the level of this or that nuerotransmitter is erroneous. I feel many of us have an endocrine disorder. Maybe HPA axis problem or something else abnormal in the endocrine system. It is so frustrating waiting and waiting for some insight into the underlying imbalances of mood disorders. To me I see the monoaminergic theories as being a big detriment to advancement. Thanks for the opportunity to vent.
> Thanks for all the information. I think I understand now. BUT, if Nardil, parnate and marplan are all MAO-a and b and affect the same neurotransmitters, why do they affect people so differently? ie, I hear parnate described as activating and nardil described as good for anxiety. What causes the difference? I would think if parnate also affects serotonin then it would be OK for people with anxiety disorders to take it, but perhaps I am wrong.
>
> Thanks everybody, for taking the time to educate me. RS
This is the end of the thread.
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