Posted by vanvog on May 9, 2013, at 8:40:20
In reply to Re: Optimal Parnate Dosing times, posted by Tyrannosaur on May 8, 2013, at 18:02:18
> Official prescribing information from GlaxoSmithKline: "Tranylcypromine differs from other MAO inhibitors in being a reversible inhibitor"
>
> Although 99,9% of relevant pages on the net seem to agree that Parnate is irreversible. Hmm.
>
>
You could have quoted the whole paragraph:
"Tranylcypromine differs from other MAO inhibitors in being a reversible inhibitor. When
tranylcypromine is withdrawn, monoamine oxidase activity is generally restored within a
week, although the drug is excreted in 24 hours."
A week!
"Return of MAO activity is more rapid after tranylcypromine is discontinued than after phenelzine is stopped, which may reflect slow reversibility, rather than complete irreversibility, of its action on the enzyme."
(found in Drug Interactions in Psychiatry, Domenic A. Ciraulo)
"Parnate is not 100% irreversible and has a shorter half life of MAO inhibition than Nardil does. However, Parnate still binds far longer and more tightly than does the reversible MAOI moclobemide, for instance. Marplan is similar to Nardil in this regard, but I am not sure exactly how selegiline compares." (another babble user)
I found a very good, easy to understand explanation of the whole process by another babble user, Larry:
"Every day, every hour, your body churns out a little bit of the enzyme monoamine oxidase. At about the same rate as it is synthesized, some of it is destroyed/recycled back to the constituent amino acids. So, at any point in time, the total amount of this enzyme is relatively constant, as the rate of formation is roughly equal to rate of destruction. That's called a dynamic equilibrium. The whole cycle is thought to take as little as two weeks, but might be a little longer.
There are some drugs that interact with the MAO enzyme, inhibiting its "designed" activity, which is to break down monoamine neurotransmitters, and similar. Inhibitors fall into two broad classes, the reversible and the irreversible. A reversible inhibitor binds to the enzyme in such a way as to block its action, but it does not affect the molecular structure. If the inhibitor breaks contact with the MAO, then its inhibition is reversed. The fully functional MAO enzyme can go back to what it was intended to do. It's like somebody parking their car in your spot. You can't park there until it moves on. Moclobemide is one such inhibitor.
In contrast, some inhibitors change the function of the MAO by chemical disruption. They either permanently bond to the enzyme active site, or damage it and leave. In either case, the enzyme cannot function. The inhibition is irreversible. Like frying an egg.
Recall, though, that I said your body churns out a little bit of MAO every hour. If the newly formed MAO does not encounter an inhibitor, it can immediately start to function. Of course, the total MAO effect also relies on the accumulated enzyme concentration over a few weeks of normal production. So, if you stop taking an irreversible inhibitor, the concentration of functional MAO will gradually build. After a week or so, the total MAO activity will be perhaps a half of normal. By two weeks or so, it will have gotten back pretty much to normal."
poster:vanvog
thread:1043363
URL: http://www.dr-bob.org/babble/20130501/msgs/1043423.html