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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Cecilia on August 1, 2007, at 22:28:34
Anyone know anything about this new drug (Prestiq)? I just read it got an "approvable" letter and "might" be approved in 2008. It claims it helps both depression and menopausal symptoms-seems unlikely considering the closely related drug, Cymbalta causes hot flashes in many people. Is it an isomer (or one of those other "tweakings" to keep the patent) of Effexor? Cecilia
Posted by SadDoggie on August 1, 2007, at 23:35:59
In reply to Prestiq (Desvenlafaxine Succinate), posted by Cecilia on August 1, 2007, at 22:28:34
That's great, and yes it's an isomer, or very related to Effexor. Since Effexor helps me I'm hoping with a little luck this might be a little better. By the way if it's "Approvable" that means the FDA approved it. This means it should be coming out in 2008, hopefully the first half.
Posted by Cecilia on August 2, 2007, at 1:31:01
In reply to Re: Prestiq (Desvenlafaxine Succinate), posted by SadDoggie on August 1, 2007, at 23:35:59
Yeah, I thought it was probably a way to extend the patent on Effexor. Effexor was intolerable for me, so I doubt this would be any different. Approvable doesn't mean approved, it means it MAY be approved, approvable drugs are sometimes denied in the end. (Who knows how the FDA thinks, considering the number of drugs like Vioxx and Phen-fen that HAVE been approved and later proved deadly.) Cecilia
Posted by kaleidoscope on August 6, 2007, at 15:05:45
In reply to Re: Prestiq (Desvenlafaxine Succinate), posted by Cecilia on August 2, 2007, at 1:31:01
Hi
Desvenlafaxine is an active metabolite of venlafaxine. Prestiq is a patent-extender. It was invented to make lots of money, not to benefit patients. Even the manufacturer hasn't been able to come up with any possible advantages that it might have over Effexor. It's a shame that Wyeth didn't decide to invest money into a novel drug which might actually benefit someone..... but then that would be difficult and might not make as much profit.
Prestiq will be an effective AD....... but will present all the same problems as Effexor. Patients who have had side effects from, or who have not benefitted from Effexor will almost certainly find that Prestiq is no better.
K
Posted by Larry Hoover on August 6, 2007, at 15:51:40
In reply to Re: Prestiq (Desvenlafaxine Succinate) » Cecilia, posted by kaleidoscope on August 6, 2007, at 15:05:45
> Prestiq will be an effective AD....... but will present all the same problems as Effexor. Patients who have had side effects from, or who have not benefitted from Effexor will almost certainly find that Prestiq is no better.
>
> KO-desmethyl-venlafaxine, or desvenlafaxine, is the product of cytochrome 2D6 action on the parent molecule......and I've been pondering this for a while.....but I wonder if Pristiq might not be of benefit to that 1 in 10 of us with little or no 2D6 activity.
A parallel situation may exist in e.g. the codeine/morphine pair. Codeine is O-desmethylated by 2D6 to morphine, making codeine a de facto time release form of morphine, but if and only if you have substantial 2D6 activity. People like me, with little or no 2D6 action, get all of the side effects of codeine but none of the benefits of morphine.
If a similar pattern holds, then Pristiq might be worth a trial by people who could not tolerate Effexor.
Just my thoughts....
Lar
Posted by Cecilia on August 6, 2007, at 20:24:21
In reply to Re: Prestiq (Desvenlafaxine Succinate) » kaleidoscope, posted by Larry Hoover on August 6, 2007, at 15:51:40
Is there a test that there is any chance the average doctor would be willing/able to do that tells you whether you have 2D6 action? Cecilia
Posted by Larry Hoover on August 7, 2007, at 9:46:08
In reply to Re: Prestiq (Desvenlafaxine Succinate) » Larry Hoover, posted by Cecilia on August 6, 2007, at 20:24:21
> Is there a test that there is any chance the average doctor would be willing/able to do that tells you whether you have 2D6 action? Cecilia
No, unfortunately. There are some labs which claim to test 2D6 function, but as far as I can tell, they actually test for specific DNA strands. Last time I checked, there were 118 different forms of the 2D6 gene, and more being reported all the time. Existing methods only check for a handful among the hundreds, making false negatives very likely. If your own gene did turn up on the test, though, the results are iron-clad. One newly developed test trumpets that it detect 13 variants, but as I mention, nearly ten times that many are known already. And those are only the ones that we've troubled ourselves to identify.
The only really useful test would be to monitor the breakdown of a known 2D6 substrate. I think they once used dextromethorphan for this, and measured the hourly concentration of the metabolite in urine. I don't know of any lab doing this today, but this method provides truly practical information. It doesn't matter what genes you've got. It matters how they are working.
Lar
Posted by kaleidoscope on August 7, 2007, at 13:25:01
In reply to Re: Prestiq (Desvenlafaxine Succinate) » kaleidoscope, posted by Larry Hoover on August 6, 2007, at 15:51:40
Hi Lar
Good to hear from you as always.
As far as I know, venlafaxine itself and desvenlafaxine have similar activity.
According to Wyeth...
'Preclinical studies have shown that venlafaxine and its major metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of serotonin and noradrenaline reuptake.'
I assume that Effexor would be an effective AD even in patients who have little 2D6 activity. I could be wrong though!
>A parallel situation may exist in e.g. the codeine/morphine pair. Codeine is O-desmethylated by 2D6 to morphine, making codeine a de facto time release form of morphine, but if and only if you have substantial 2D6 activity. People like me, with little or no 2D6 action, get all of the side effects of codeine but none of the benefits of morphine.
Why all the side effects Lar? Many of the side effects of codeine are presumably caused by the morphine metabolite.
Codeine generally has a rapid onset and a short duration of action (4 hours at most for analgesia - although some side effects may last longer). In this sense, it is quite unlike modified-release morphine. I assume that a high percentage of a dose of codeine is converted to morphine via first-pass metabolism, although this is essentially a guess :)
Hope you are doing well Lar and your pain is better controlled.
Take care
Posted by Larry Hoover on August 7, 2007, at 18:32:00
In reply to Re: Prestiq (Desvenlafaxine Succinate) » Larry Hoover, posted by kaleidoscope on August 7, 2007, at 13:25:01
> Hi Lar
>
> Good to hear from you as always.And you.
> As far as I know, venlafaxine itself and desvenlafaxine have similar activity.
>
> According to Wyeth...
>
> 'Preclinical studies have shown that venlafaxine and its major metabolite, O-desmethylvenlafaxine (ODV), are potent inhibitors of serotonin and noradrenaline reuptake.'
>
> I assume that Effexor would be an effective AD even in patients who have little 2D6 activity. I could be wrong though!But what if the adverse effects (leading to intolerability) arise from alternate metabolites, i.e. those not arising from the O-desmethyl metabolite. I'm speculating, but desmethylation improves the kidney's ability to sequester the molecules into urine. Being unable to do so would potentially lead to both higher parent molecule concentrations (by retention) and alternate metabolites (by diversion), in comparison to those who can do so. Either one might lead to lowered tolerability, notwithstanding efficacy against depression.
> >A parallel situation may exist in e.g. the codeine/morphine pair. Codeine is O-desmethylated by 2D6 to morphine, making codeine a de facto time release form of morphine, but if and only if you have substantial 2D6 activity. People like me, with little or no 2D6 action, get all of the side effects of codeine but none of the benefits of morphine.
>
> Why all the side effects Lar? Many of the side effects of codeine are presumably caused by the morphine metabolite.Well, this study sums it up quite nicely: http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=9696456
In rats, the glucoronidated conjugate has some analgesic activity, but as far as I can tell, that has not been shown to be the case in humans, controlling for 2D6 activity.
> Codeine generally has a rapid onset and a short duration of action (4 hours at most for analgesia - although some side effects may last longer). In this sense, it is quite unlike modified-release morphine.I meant to focus on the prodrug function, which would not literally equate with IR morphine. It would be somewhat intermediate, I should think.
> I assume that a high percentage of a dose of codeine is converted to morphine via first-pass metabolism, although this is essentially a guess :)
Well, somewhere between none to 17%, from what I've read. And it wouldn't all be first pass conversion.
> Hope you are doing well Lar and your pain is better controlled.
Neither is true, I'm sorry to reveal.
> Take care
>
>And you, E.
Lar
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