Posted by Tomatheus on January 8, 2006, at 0:12:19
In reply to Re: Moclobemide-does it really work for sombody here?, posted by sdb on January 6, 2006, at 19:04:52
> But what I am angry about is, that the doc of moclobemide promises you just inpossible things. I am wondering about the statement "very good improvement in depression in just 7 days", how it is possible with such low dosages in that short time with a weak reversible mao?
sdb,
Even though I question moclobemide's ability to produce a "very good improvement in depression" in most patients at a low dose, I do think that this improvement (if it were to actually happen) would likely become apparent within a week, if not sooner. How could this be possible? Unlike the irreversible MAOIs (e.g., Nardil and Parnate), moclobemide is extremely short-acting. Because Nardil and Parnate are irreversible, the "effects" of just one dose of either of these medications last for approximately two weeks. So, for every dose of Nardil or Parnate that a patient takes during the first two weeks of treatment, the amount of MAO inhibition in the brain (and elsewhere) rises by a certain percentage. Finally, after approximately two weeks at a given dose of Nardil or Parnate, the percentage of MAO inhibition in the brain stops rising and reaches a relatively constant level.
With moclobemide, the percentage of MAO inhibition produced by one dose returns to 100 percent after only 16 hours (Nair et al. 1993) - and remember, this is in comparison to two weeks with Nardil and Parnate. This, of course, is due to moclobemide's reversibility. Instead of binding to the MAO enzymes until they lose their functionality, moclobemide only binds to the enzymes (well, in this case just MAO-A) temporarily. Considering that it takes less than a day for the percentage of MAO inhibition from one dose of moclobemide to return to 100 percent, the percentage of MAO-A inhibition produced by moclobemide doesn't continue to rise each day for two weeks until it reaches a constant level of MAO-A inhibition. At most, it would only take a few days for this to happen on moclobemide. From what I can tell, it seems that most MAOIs (if not all MAOIs) begin exerting their therapeutic effects once the percentage of MAO inhibition reaches a constant level. So, because it doesn't take very long for this constant level to be reached on moclobemide, it begins working relatively quickly (i.e., within a week).
Now, I would also argue that the "constant level" of MAO-A inhibition produced by moclobemide is not actually all that constant, especially at the lower doses. I should make it clear that when I said that moclobemide's percentage of MAO-A reaches a "constant level" after a few days at most, I was referring to the fact that the range of MAO-A inhibition does not change from one day to the next. So, if the percentage of MAO inhibition ranged from 30 percent to 80 percent within the course of a day, the MAO-A inhibition would be at a "constant level" (as I described it) if the range of MAO inhibition were to remain the unchanged (still ranging from 30 percent to 80 percent) the following day. As I'm sure you can see, what I described as a "constant level" of MAO-A inhibition is still anything but constant because the level of MAO-A inhibition still varies considerably over the course of a day (btw, the figures of 30 percent and 80 percent are just percentages that I made up to illustrate the fact that the percentage of MAO-A inhibition provided by moclobemide could vary significantly over a given period of time). I'm just hypothesizing here, but I have reason to suspect that this variability in MAO-A inhibition is at least part of the reason why moclobemide tends to be rather ineffective in practice. If you're looking to get any kind of therapeutic response from moclobemide, I think that your best bet would be to take a high daily dose (e.g., 900-1200 mg/day) and to space your doses throughout the day as much as you possibly can. This way, you'll be getting more consistency in moclobemide's MAO-A inhibition than you could get from taking a lower dose and/or taking all of the pills at the same time each day.
Of course, I'm not suggesting that your results will be guaranteed if follow what I described as your "best bet." I tried doing the same thing myself and got no response. But I do think that your likelihood of getting a response would be at its highest if you go with a high daily dose and space your doses out throughout the day.
I hope this makes at least some sense to you. If not, let me know, and I'll try to explain it better.
Tomatheus
==
REFERENCE
Nair, N. P. V., Ahmed, S. K., & Ng Ying Kin, N. M. K. (1993). Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: Focus on moclobemide. Journal of Psychiatric Neuroscience, 18, 214-25.
poster:Tomatheus
thread:594410
URL: http://www.dr-bob.org/babble/20051231/msgs/596444.html