Posted by chemist on April 25, 2005, at 10:32:29
In reply to Re: Effects of Selegiline's amphetamine metabolites? » cache-monkey, posted by Sarah T. on April 25, 2005, at 2:16:23
> Hi cache-monkey. All I know about buproprion is that I was on it for a long time, and I had terrible insomnia, high blood pressure, palpitations and anxiety, in spite of what the drug company literature advertised at that time. I also know that, among other things, bupropion is a potent inhibitor of the 2D6 liver enzyme, and that hydroxybupropion is a substrate of that same enzyme. In the other words, the drug inhibits its own metabolism! If you happen to have a fairly robust version of that enzyme in your liver, then I guess you can handle the medicine well. On the other hand, if you're like me (a poor metabolizer), then taking a drug that inhibits its own metabolism is going to be very unpleasant, if not downright dangerous.
hello there, chemist here...bupropion is a major substrate of the cyp-2B6 isoenzyme, and a weak inhibitor of 2D6. the 3 active metabolites are reported to exhibit activities rangin from 20% to 50% or the parent compound. the drug does not inhibit its own metabolism, nor does it autoinduce. the majority of drugs are metabolized (those that go the hepatic route) by the 2D6 isoenzyme, and if you are caucasian, there is a 7 to 10% chance your are a poor-metabolizer in re: the 2D6. the metabolic route for bupropion is via phase I, and the hydroxy derivative is half as active as the parent and, further, is metabolized by the 2B6 (not 2D6). given the large difference in K_{i}, it is unlikely though possible that some competitive binding is at play, although a more reasonable scenario is that use of another drug with similar affinity for 2B6 - paroxetine, sertraline, theophylline etc. - is responsible for increased serum concentration of the parent and the adverse effects associated with the increase...all the best, chemist
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