Posted by JohnX2 on October 26, 2001, at 0:59:38
In reply to Re: medication poop-out questionaire » JGalt, posted by JohnX2 on October 26, 2001, at 0:50:45
From medline, beware of drug interactions.
Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe.
J Clin Pharmacol 2001 Apr;41(4):443-51 (ISSN: 0091-2700)Amchin J; Ereshefsky L; Zarycranski W; Taylor K; Albano D; Klockowski PM [Find other articles with these Authors]
Wyeth-Ayerst Laboratories, 240 North Radnor-Chester Road, St. Davids, PA 19087, USA.Two antidepressants, venlafaxine and fluoxetine, were evaluated in vivo for their effect on cytochrome P450 2D6 (CYP2D6) activity, measured by the ratio of
dextromethorphan, a sensitive CYP2D6 marker, to its metabolite dextrorphan (i.e., DM:DT) excreted in urine after DM coadministration. Twenty-eight healthy extensive
metabolizers of CYP2D6 received either venlafaxine (37.5 mg bid for 7 days, then 75 mg bid until Day 28) or fluoxetine (20 mg daily for 28 days); 26 completed the study.
Plasma concentrations of both drugs and their active metabolites were determined. DM:DTs were evaluated at baseline (Day 0), on Days 7 and 28 of dosing, and 2 weeks after
drug discontinuation (Day 42). Steady-state drug and metabolite levels were achieved in both groups by Day 28. Mean DM:DTs for venlafaxine and fluoxetine differed statistically
significantly (p < 0.001) on Days 7, 28, and 42. Comparisons of DM:DT as a percentage of baseline values showed that DM:DT increased 1.2-fold for venlafaxine and 9.1-fold for
fluoxetine on Day 7 (p < 0.001) and increased 2.1-fold for venlafaxine and 17.1-fold for fluoxetine on Day 28 (p < 0.001). Inhibition of CYP2D6 metabolism persisted for 2
weeks after discontinuation of fluoxetine, unlike the case with venlafaxine. These in vivo results confirm in vitro data demonstrating significantly weaker inhibition of CYP2D6 with
venlafaxine than with fluoxetine. This suggests that clinically significant interactions involving CYP2D6 inhibition could occur between fluoxetine and drugs metabolized by
CYP2D6 but may be less likely to occur with venlafaxine.
>
> Interesting stuff.
>
> He is my advice about dxm, *DO NOT* take it
> with any MAOI inhibitor. Also taking things
> like yohimbine with an MAOI inhibotor is bad.
> Also yohimbine will substantially potentiate
> dxm because it interferes with its metabolism.
>
> I speak from experience. I was experiencing
> a caugh while taking
> a weird combo of remeron,manerix,selegiline,
> reboxetine and klonopin. I took a swig of
> robitussin as it helps to relieve the caugh,
> and my heart felt like it was about to
> stop beating. Scary .hit.
>
> I did find an unconventional approach to
> using dxm as a therapeutic agent described
> by a neurologist in a patent disclosure(s). The
> idea was to co-prescribe dxm with a medicine
> that inhibits its breakdown. This substantially
> increases the 1/2 life (the time for the body
> to break it down), and made it easier to use
> as a therapeutic agent for things he was treating,
> tinnitus, peripheral neuropathy, withdrawal fom
> addictive drugs.
>
> check out www.uspto.gov
> look up patents 5,863,927
> also 6,207,674.
>
> I'm not sure why he has patented this. Would
> one need to send him a royalty if they used it? ;)
>
> He suggests quinidine (a heart med) as the adjunct
> to inhibit the liver enzyme, but Prozac would work
> too (do a search on Medline for fluoxetine and
> dextromethorphan and you will get a hit on the
> drug interactions). dextromethorphan is often used
> to test wheather or not another drug inhibits
> cyp450-2d6. When this happens the ratio of
> dxm:dextrophan (the metabolite) goes up substantaily.
>
> -john
>
>
> > Well I went and typed out a big long response to this, then had to confirm my registration to post, and wouldn't you know, AOL decides to quit on me during the registration. Argghh...thankfully I got something to calm me down.
> >
> > Anyway, my mom is on Lamictal and klonopin, but not the 12-hr ritalin. She is only on the startup dose (25mg eod) but says she does notice significantly more energy throughout the day. The doctor apparantly knows nothing about its NMDA properties, simply put her on it to replace topamax which was causing some ridiculous weight loss. I told her to lobby for some adderal (she's tired all the time, rather unmotivated, similiar to my own symptoms, only more severe and she doesn't care too much about the lack of energy).
> >
> > About the DXM and likewise drugs. Turns out that those Onley lesions aren't really all that bad even at the dissociative doses (well, the level 3 and 4 stages is where they seem to show up the most). Anyway, my theory is, what if these NMDA antagonists would work at non-dissociative doses. I'm thinking somewhere around 50mg of DXM, since acc. to the FAQ, 100mg seems to be the threshold dose. At this dosage, brain damage should be so small as to be inconsequential I would imagine. If you really wanted to go all out on preventing brain damage, it would seem logical that you could take something that would occupy the GABA receptors prior to taking the DXM, thus preventing the cause of the Onley's lesions, assumably selective production? of only glutamate. I believe GHB is capable of this, or perhaps 1,4 butanediol, which would be more time released (still every 4-6 hrs or so, this could present a problem if DXM completely inhibits other things from binding to the GABA). Actually there is a patent out for a GHB derivative that lasts 8-12 hrs, I could see someone making some money off that if they wanted to pursue this. That is of course, if the method of action of GHB is how I remember it (GABA agonist amongst other things)...but I'm not sure, I only remember the doc who discovered it was looking for a way to make GABA cross the blood brain barrier.
> >
> > So lamictal increases NDMA receptor sensitivity. Interesting. In some ways that may be better than DXM since it might be possible, through extended use of DXM, to decrease receptor sensitivity. I don't know. For one, I would be very interested in a drug that could increase dopamine and perhaps norepinephrine sensitivity. Perhaps this is what tricyclics are supposed to do, I don't know, I never studied them too much due to their supposed dumbing down effects. In any case, I'm sure something more effective could be found for them. Combining something like that with selegiline and lamictal and low dose adderal would seem like it would be the ultimate antidepressant in theory.
> >
> > Of course, then again, maybe it will happen with extended use that glutamate will 1. become depleted in the brain or 2. have its receptors decreased in number or sensitivity. If that is the case, our body's chemistry is really against us, and our only hope for indefinite long term freedom from depression/melancholy, etc. will be the genetic engineering as described in the Hedonistic Imperitive.
> >
> > Best Regards,
> > John Galt
poster:JohnX2
thread:81909
URL: http://www.dr-bob.org/babble/20011025/msgs/82323.html