Posted by King Vultan on September 26, 2004, at 9:46:18
In reply to Re: moclobemide??, posted by woolav on September 25, 2004, at 13:51:30
Moclobemide is a reversible inhibitor of MAO-A, the variety of monoamine oxidase that is mainly responsible for metabolizing serotonin and norepinephrine. There are several advantages to this from a safety standpoint. One is that because it's reversible, when the dreaded tyramine from some cheddar cheese comes around, the moclobemide can detach from the MAO-A molecule and allow the MAO to gobble up the tyramine. Another is that because moclobemide does not affect MAO-B, this enzyme is still available to metabolize tyramine. Yet another is that if treatment of moclobemide is discontinued, MAO-A activity returns to normal much more quickly than it does after ending treatment with an irreversible MAO inihibitor like Nardil or Parnate, which render the MAO molecules they bind to (which includes both MAO-A and B because Nardil and Parnate are also nonselective) permanently useless.
In practice, however, the ease with which moclobemide detaches from the MAO-A also implies that there is a possibility it may also detach in the presence of serotonin or norepinephrine. If that happens, the MAO-A is no longer being inhibited from an antidepressant standpoint and is able to carry out its normal function of wiping out serotonin and norepinephrine molecules. It's believed this does actually happen to some extent, not enough to prevent moclobemide from being an effective antidepressant, but probably one that does not have as robust an effect as Nardil, for instance, where any MAO molecule it binds to is out of commission forever.
The availability of MAO-B during moclobemide treatment to metabolize tyramine winds up not being much of a plus, because while both types of MAO have the ability to metabolize tyramine, 70% of the MAO in the gut is MAO-A, and this form winds up being by far the most important in relation to tyramine and resultant hypertensive reactions. However, the ease with which MAO-A activity returns to normal after cessation of moclobemide treatment is a real plus. According to "Clinical Advances in Monoamine Oxidase Inhibitor Therapies", normalization of the tyramine pressor response (the "cheese effect") was found to be approximately 3 days in a 1991 study (Bieck, et al).
Todd
poster:King Vultan
thread:394626
URL: http://www.dr-bob.org/babble/20040921/msgs/395248.html