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Re: CAM: SSRIs and Our Body's Synthesis of Serotonin BobS.

Posted by Cam W. on December 21, 2001, at 0:12:21

In reply to Re: CAM: SSRIs and Our Body's Synthesis of Serotonin, posted by BobS. on December 20, 2001, at 19:18:28

Bob - I do know that they do test for it. I haven't seen the original study, so I don't know exactly how they do it, but I am certain they know where the gene is, I have read many reviews quoting that 5% of those of European decent (us honkies) are polymorphic. This would mean that any drug metabolized by CYP-2D6 would be metabolized faster. The problem with my theory is that Effexor is also metabolized, to a lesser extent, by CYP-3A4, CYP-2C19, and CYP-1A2. CYP-2D6 metabolizes venlafaxine to the equally active O-desmethylvenlafaxine (ODV).

I did read a article in which poor and extensive metabolizers of CYP-2D6 were tested in vitro (ie. not in living people, but in test tubes with a little and a lot of the CYP-2D6 enzyme to see if there was any difference in metabolic rate. The study concluded that there wasn't any difference in total exposure "to the sum of the two active species" (ie. venlafaxine and ODV).

So, what the above means is that both venlafaxine and ODV are active to a similar extent, in a test tube. This does not take into account the real life situation where ODV is peed off twice as fast as venlafaxine. So, since the in vitro study did not separate venlafaxine from ODV (they didn't think they had to because both molecules have similar potency). Since the extensive metabolizers produce more ODV sooner, they would pee more of this metabolite out, more quickly, than would the poor metabolizers. Therefore, extensive metabolizers should rid the body of venlafaxine faster.

Anyway, yes there is a way to test for CYP-2D6 polymorphism, I just don't know how or where you would get it done.

(Sorry for thinking out loud above) - Cam




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