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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 10 of 10. This is the beginning of the thread.
Posted by JohnX2 on November 4, 2001, at 23:36:24
Cam et. al,I found this website with information on memantine.
It compares the binding affinities of various
nmda blockers. It acknowledges that the testing
results were only rough guidlines:http://www.pano.com/Products/Memantine/body_memantine.html
Also gives a nice little summary of all the various
little clinical trials.One thing is interesting in Table1.
Of the low affinity inhibitors (the non-competitive
and less toxic ones), dextrophan showed substantially
greater affinity than memantine and then came
dextromethorphan.dizcolipine (Mk-801 worst case) > > > > >
dextrophan > memantine > dextromethorphan.Due you think this makes dxm less toxic
if it's plasma ratio dextromethorphan:dextrophan
was manipulated up. And do you think this would have
a substantial effect on therapeutic results?-john
Posted by JohnX2 on November 4, 2001, at 23:41:51
In reply to dextrophan vs. dextromethorphan CAM, posted by JohnX2 on November 4, 2001, at 23:36:24
my spelling is atrocious.
I hope this doesn't offend anyone.
I say we change the spelling rules
on pbabble. For example, I would like to rename
Adderall Aderal.
>
> Cam et. al,
>
> I found this website with information on memantine.
> It compares the binding affinities of various
> nmda blockers. It acknowledges that the testing
> results were only rough guidlines:
>
> http://www.pano.com/Products/Memantine/body_memantine.html
>
> Also gives a nice little summary of all the various
> little clinical trials.
>
> One thing is interesting in Table1.
>
> Of the low affinity inhibitors (the non-competitive
> and less toxic ones), dextrophan showed substantially
> greater affinity than memantine and then came
> dextromethorphan.
>
> dizcolipine (Mk-801 worst case) > > > > >
> dextrophan > memantine > dextromethorphan.
>
> Due you think this makes dxm less toxic
> if it's plasma ratio dextromethorphan:dextrophan
> was manipulated up. And do you think this would have
> a substantial effect on therapeutic results?
>
> -john
Posted by JGalt on November 5, 2001, at 15:54:50
In reply to Re: dextrophan vs. dextromethorphan CAM, posted by JohnX2 on November 4, 2001, at 23:41:51
Hey John...Well the article itself states that those with lower affinities are almost always safer, so I would say that, yes, it would be safer with a higher ratio DXM:DXO
Of course the article itself states that drugs with lower receptor affinities are less toxic in general, so it seems likely that that is true. Also, I headed on over to the dxm faq and did some reading up on the conversion process DXM > > DXO and they state that it is primarily done by the CYP 2D6. They suggest that this conversion can be reduced by a number of things, including:
taking Dextromethorphan polistirex instead of DXM HBr
injecting DXM instead of using it orally
taking it with a CYP2D6 inhibitors.To look over everything they said, go here:
http://www.lycaeum.org/drugs.old/synthetics/dxm/faq/general_info.html and scroll down to 4.3 for the stuff I was talking about.To look at a small list of CYP2D6 inhibitors, go to:
http://www.lycaeum.org/drugs.old/synthetics/dxm/faq/appendices.html#toc.15.1(there's quite a lot of them, including prozac and antihistamines)
They also back up that DXO binds more to the NMDA receptor than DXM (which they say binds more to the PCP2 and sigma receptors).
Posted by JohnX2 on November 5, 2001, at 16:23:58
In reply to Re: dextrophan vs. dextromethorphan CAM, posted by JGalt on November 5, 2001, at 15:54:50
Supposedly the dextrorphan doesn't readily
cross the blood-brain barrier (but how much so)
and the dxm quickly converts to dextrorphan
rather quickly. Hence motivation to inhibit
the conversion.thnkx,
john
> Hey John...Well the article itself states that those with lower affinities are almost always safer, so I would say that, yes, it would be safer with a higher ratio DXM:DXO
>
> Of course the article itself states that drugs with lower receptor affinities are less toxic in general, so it seems likely that that is true. Also, I headed on over to the dxm faq and did some reading up on the conversion process DXM > > DXO and they state that it is primarily done by the CYP 2D6. They suggest that this conversion can be reduced by a number of things, including:
> taking Dextromethorphan polistirex instead of DXM HBr
> injecting DXM instead of using it orally
> taking it with a CYP2D6 inhibitors.
>
> To look over everything they said, go here:
> http://www.lycaeum.org/drugs.old/synthetics/dxm/faq/general_info.html and scroll down to 4.3 for the stuff I was talking about.
>
> To look at a small list of CYP2D6 inhibitors, go to:
> http://www.lycaeum.org/drugs.old/synthetics/dxm/faq/appendices.html#toc.15.1
>
> (there's quite a lot of them, including prozac and antihistamines)
>
> They also back up that DXO binds more to the NMDA receptor than DXM (which they say binds more to the PCP2 and sigma receptors).
Posted by Elizabeth on November 8, 2001, at 19:55:58
In reply to dextrophan vs. dextromethorphan CAM, posted by JohnX2 on November 4, 2001, at 23:36:24
This thread reminded me of something I'd been meaning to ask about.
I've taken dextromethorphan three times. One of these times, I wasn't taking any other psychoactive meds; one, I was taking Klonopin 1mg tid; and a few days ago, I took it with my current cocktail (desipramine 200mg, buprenorphine 0.9mg, and Trileptal 300mg per day, and Xanax 2mg prn). All three times I took 30mg of dextromethorphan (two times it was in the form of Coricidin HBP, a tablet which also contains 4mg of chlorpheniramine; the other time it was Robitussin Maximum Strength, with no other active ingredients except DXM).
All three times, I got seriously f---ed up a few hours after taking the cough medicine, but I still had a cough! The intoxication lasted for about 36 hours. I've also recently discovered that I appear not to be metabolizing the desipramine properly, in case this is relevant. Any idea what's up? And how I can get rid of my cough??? (Buprenorphine doesn't seem to help either.)
-elizabeth
Posted by JohnX2 on November 8, 2001, at 21:04:54
In reply to Re: DXO vs. DXM (sidetrack) - Cam?, posted by Elizabeth on November 8, 2001, at 19:55:58
Have you been screened to see if you are a
poor metabollizer of cyp450-2d6 (converts the
dxm and many other meds). 5-7% of the caucasion
population has this problem and it could
seriously impact metabolization of many meds
(I don't know off hand if desipramine goes this
route).As far as anti-tussives go, I'll check with
my pharmacist friend and see what he recommends.ps. this is totally offbeat, but I have read
anecdotal experiences on dxm web pages suggesing not
to take Corcidin branch dxm for whatever reason.
Do you have problems with the more standard
Robitussin-DM?Regards,
john
> This thread reminded me of something I'd been meaning to ask about.
>
> I've taken dextromethorphan three times. One of these times, I wasn't taking any other psychoactive meds; one, I was taking Klonopin 1mg tid; and a few days ago, I took it with my current cocktail (desipramine 200mg, buprenorphine 0.9mg, and Trileptal 300mg per day, and Xanax 2mg prn). All three times I took 30mg of dextromethorphan (two times it was in the form of Coricidin HBP, a tablet which also contains 4mg of chlorpheniramine; the other time it was Robitussin Maximum Strength, with no other active ingredients except DXM).
>
> All three times, I got seriously f---ed up a few hours after taking the cough medicine, but I still had a cough! The intoxication lasted for about 36 hours. I've also recently discovered that I appear not to be metabolizing the desipramine properly, in case this is relevant. Any idea what's up? And how I can get rid of my cough??? (Buprenorphine doesn't seem to help either.)
>
> -elizabeth
Posted by Cam W. on November 8, 2001, at 22:25:05
In reply to Re: DXO vs. DXM (sidetrack) - Cam?, posted by Elizabeth on November 8, 2001, at 19:55:58
Elizabeth - Hmmm...so by f***ed up, what do you mean. Anticholinergic dry mouth, dizziness, visual accomodation problems; or is it "walking on cornflakes, waiting for the band to come", kinda different, headspace (if ya know what I mean; sort of a detached feeling).
If it's the first, it's the desipramine; if it's the second, it's the dextromethorphan. Desipramine can exagerrate the CNS depressants, like DM; or by itself the DES's anticholinergic effects could be potentiated. If I had to chose, I'd pick the exagerrated CNS depressant effects. You see that detached, spacey thing when DM metabolism is inhibited by fluoxetine.
Now, for the cough. Is it dry and hacky or productive (ie. trying to bring up mucus). In either case, increase liquid (ie. water) intake and pee off the bug causing it, and steam to moisturize the tissues of a dry cough and to loosen the mucus of a productive cough.
In a productive cough, you really don't want to stop the cough (well, you do want to stop it, but you shouldn't). A productive cough is trying to get rid of the mucus in the lungs. It is worse at night because you change to a prone position and the mucus changes orientation, triggering the cilia in the lungs as it flows over new areas. It sometimes helps to prop yourself up in bed and sleep in a semi-sitting position (the mucus doesn't change orientation, as much). Also, you can take straight Robitussin™ (guaifenesin) which breaks the sulphur bonds in the mucus, making it easier to cough out. You have to saturate the lung tissue (ie. drink plenty of fluids and steam) or the mucus may stick in smaller pieces. If you don't have a steamer, just sit in the bathroom with a magazine or journal article, close the door, and run a hot shower.
God, I hope it's a productive cough; that was a lot of typing.
As for a dry cough, you're screwed. What you can do is the liquids and steam thing. Also suck on Fisherman's Friend lozenges (orignal - white package)(Altoids can be substituted, but F.F. works better).
I hope this helps. - Cam
P.S. John, thanks for the vote of confidence, dude (I am a community pharmacist).
Posted by Elizabeth on November 9, 2001, at 13:16:51
In reply to Re: DXO vs. DXM (sidetrack) » Elizabeth, posted by Cam W. on November 8, 2001, at 22:25:05
Hi John and Cam. Thanks for responding.
John:
> Have you been screened to see if you are a
poor metabollizer of cyp450-2d6 (converts the
dxm and many other meds).I'm familiar with that, and while I've never been tested for it, I probably do have that polymorphism (I'm a poor metabolizer of tricyclics).
> As far as anti-tussives go, I'll check with
my pharmacist friend and see what he recommends.I've used one called Tessalon before -- it's okay to use with MAOIs -- but it requires a script.
> ps. this is totally offbeat, but I have read
anecdotal experiences on dxm web pages suggesing not to take Corcidin branch dxm for whatever reason.People using DXM recreationally take large doses. I mean monster doses, like chugging down a whole bottle of Robitussin at once. (GROSS!) Coricidin-HBP, the kind I used, has 4 mg of chlorpheniramine, an antihistamine, in each tablet; taking a whole lot of chlorpheniramine can be dangerous.
> Do you have problems with the more standard
Robitussin-DM?Never tried it. It has extra ingredients that I don't need or want, and it offers no advantage over Robitussin-Max.
Cam:
> Elizabeth - Hmmm...so by f***ed up, what do you mean. Anticholinergic dry mouth, dizziness, visual accomodation problems; or is it "walking on cornflakes, waiting for the band to come", kinda different, headspace (if ya know what I mean; sort of a detached feeling).I don't remember having any anticholinergic side effects with it either of the first two times I took it. The third time (a few days ago), I was also taking buprenorphine, which causes pretty bad dry mouth and constipation, so it's hard to say. But I've taken chlorpheniramine by itself many times (bupe also causes severe itching) and it doesn't cause any noticeable side effects for me in doses up to 16 mg.
I'm a little bit, uh, *puzzled* by the other possible definition you gave for "f---ed up." (I don't recognize the quote, sorry.) I was very dizzy and ataxic. My thoughts were also racing in unexpected directions. I was unable to sleep. Time seemed to be passing faster some times and slower others. I tried to take my blood pressure but my pulse was too weak or something. (I have a digital BP monitor; it kept giving me "E" for "error" -- that's what it does when it can't get a reading.) Does that give you some idea? My pupils were also dilated even though I had taken buprenorphine too.
> If it's the first, it's the desipramine; if it's the second, it's the dextromethorphan.
This wasn't tricyclic toxicity.
> Desipramine can exagerrate the CNS depressants, like DM;
It really didn't feel like a CNS depressant.
> You see that detached, spacey thing when DM metabolism is inhibited by fluoxetine.
I'm not sure about detached but it was definitely spacey!
> Now, for the cough. Is it dry and hacky or productive (ie. trying to bring up mucus).
Dry, nonproductive.
> In either case, increase liquid (ie. water) intake and pee off the bug causing it, and steam to moisturize the tissues of a dry cough and to loosen the mucus of a productive cough.
Showering helps some. I always try to drink as much as I can because of the dry mouth and constipation from the bupe.
> Also, you can take straight Robitussin™ (guaifenesin) which breaks the sulphur bonds in the mucus, making it easier to cough out.
That doesn't work for dry coughs, which is why I didn't choose a product with guaifenesin in it.
> God, I hope it's a productive cough; that was a lot of typing.
Sorry dude! < g >
> As for a dry cough, you're screwed. What you can do is the liquids and steam thing. Also suck on Fisherman's Friend lozenges (orignal - white package)(Altoids can be substituted, but F.F. works better).
What's the active ingredient?
Shouldn't opioids suppress the cough reflex, whether it's dry or wet? The bupe isn't helping at all, and I'm wondering if it's because it's a partial/mixed agonist.
> P.S. John, thanks for the vote of confidence, dude (I am a community pharmacist).
I agree with him. (Hey, you said "dude." I thought I was the only person here who used that word.)
-elizabeth
Posted by Cam W. on November 9, 2001, at 22:30:49
In reply to Re: DXO vs. DXM (sidetrack), posted by Elizabeth on November 9, 2001, at 13:16:51
Elizabeth - I really don't know what you can do about a cough; especially after checking my files and finding the following article in the Western Journal of Medicine:
It sounds like you unfortunately took a "fun" dose of DM. I wonder if the DES or BUPH inhibited it's metabolism, somehow; or if it had an additive effect with the BUPH. It shouldn't, but I've been wrong before.
Fisherman's Friend really has no "active" ingredients, just a little eucalyptus and menthol; but it works! Opiods that block the receptors in the cough center of the brainstem would probably work better than BUPH (ie. the lack of cougn control activity may have something to do with the agonist activity).
I'm not sure that you wouldn't get a antitussive effect with codeine (aside from the low doses talked about in the above article) or hydrocodone. You may also get the same exaggerated effect seen the DM. You could try lowering the DM dose to about a quater to a half and see if that works. It is always easy to titrate up, than get rid of the effect once it has happened.
The quote was from "I Am The Walrus" by the Beatles. It is about taking acid and going to a concert, where the anticipation of the band coming and sensory overrload of the crowd would make one feel even more detached from reality, than one would ordinarily be from taking acid. Hence, "sitting on a cornflake, waiting for the band to come" is imagery from this experience. I have also heard it explained as "walking on bubbles or bubble wrap".
Good luck peeing that bug out, Sweetie. - Cam
Posted by Elizabeth on November 10, 2001, at 22:38:02
In reply to Re: DXO vs. DXM (sidetrack) » Elizabeth, posted by Cam W. on November 9, 2001, at 22:30:49
Thanks! Links to articles are always welcome -- I consider my education to be a lifelong process (plus I just like reading about this stuff). I think they didn't use enough codeine -- it's pretty weak. Do other opioids help with cough, as a rule?
> It sounds like you unfortunately took a "fun" dose of DM.
(I wouldn't call it fun so much as weird. I guess it was kind of interesting.)
I took 30 mg -- the recommended dose for cough, equivalent to either 5 or 10 mL of Robitussin Max, I think. There's some indication that I'm deficient of CYP 2D6 (my desipramine levels were way high when I had them checked and rechecked); desipramine also probably competitively inhibits that enzyme, if nothing else. (Bupe is metabolized via 3A4, I think, and it doesn't affect NMDA receptors so far as I'm aware so there shouldn't have been additive effects.)
> Fisherman's Friend really has no "active" ingredients, just a little eucalyptus and menthol; but it works!
Ahh! I do have some "unmedicated" nose spray that sort of helps a little. I'll see if I can dig it up.
> Opiods that block the receptors in the cough center of the brainstem would probably work better than BUPH (ie. the lack of cougn control activity may have something to do with the agonist activity).
Buprenorphine definitely doesn't work for cough. How do I tell if a particular drug will help? Bupe is supposedly a partial mu agonist and a kappa antagonist (FWIW).
> I'm not sure that you wouldn't get a antitussive effect with codeine (aside from the low doses talked about in the above article) or hydrocodone.
Codeine doesn't work very well for me (this could also be explained by enzyme deficiency), but I'll give hydro a try. Gosh, I wonder if it would work -- does the antitussive effect have anything to do with opioid receptors? Because bupe blocks the effect of other opioids -- it clings tight to the mu receptor.
> You could try lowering the DM dose to about a quater to a half and see if that works.
The pills are hard to slip, but tonight I tried taking 1/4 pill. I seem okay so far, but it hasn't been long.
> The quote was from "I Am The Walrus" by the Beatles.
Ahh. Not my generation (although I do like a lot of Beatles songs -- "Happiness is a Warm Gun" is probably my favorite, of the ones I know).
> It is about taking acid and going to a concert, where the anticipation of the band coming and sensory overrload of the crowd would make one feel even more detached from reality, than one would ordinarily be from taking acid. Hence, "sitting on a cornflake, waiting for the band to come" is imagery from this experience. I have also heard it explained as "walking on bubbles or bubble wrap".
Well, I don't think this was a hallucinogenic trip. I mean, I wasn't seeing colors or anything.
> Good luck peeing that bug out, Sweetie. - Cam
Thanks!
-elizabeth
This is the end of the thread.
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