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
poster:Larry Hoover
thread:773437
URL: http://www.dr-bob.org/babble/20070730/msgs/774627.html