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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by cactus on May 9, 2008, at 17:13:42
I know they're very similar but what's the exact difference. I'm pretty sure armodafinil isn't available in australia but I'd like to know more about it, can anyone help explain it to me. I'm very happy with my modafinil but I'd just like to know.
I'm asking in here because as soon as I start reading about chemical structures and isotopes etc, my brain just shuts down and shiny objects start getting my attention.
Thanks everyone. C
Posted by undopaminergic on May 9, 2008, at 19:43:56
In reply to modafinil and armodafinil, how do they differ????, posted by cactus on May 9, 2008, at 17:13:42
> I know they're very similar but what's the exact difference. I'm pretty sure armodafinil isn't available in australia but I'd like to know more about it, can anyone help explain it to me. I'm very happy with my modafinil but I'd just like to know.
>
> I'm asking in here because as soon as I start reading about chemical structures and isotopes etc, my brain just shuts down and shiny objects start getting my attention.
>Modafinil is a so-called racemic mixture of equal amounts of two optical isomers, R-modafinil (armodafinil) and S-modafinil. See
http://en.wikipedia.org/wiki/EnantiomerOften a substance is first marketed as the racemic mixture, and then the pharmacologically more active isomer is introduced as a patent-extender, usually with recommended doses that are half of those of the racemate.
Posted by cactus on May 10, 2008, at 19:33:31
In reply to Re: modafinil and armodafinil, how do they differ????, posted by undopaminergic on May 9, 2008, at 19:43:56
> > I know they're very similar but what's the exact difference. I'm pretty sure armodafinil isn't available in australia but I'd like to know more about it, can anyone help explain it to me. I'm very happy with my modafinil but I'd just like to know.
> >
> > I'm asking in here because as soon as I start reading about chemical structures and isotopes etc, my brain just shuts down and shiny objects start getting my attention.
> >
>
> Modafinil is a so-called racemic mixture of equal amounts of two optical isomers, R-modafinil (armodafinil) and S-modafinil. See
> http://en.wikipedia.org/wiki/Enantiomer
>
> Often a substance is first marketed as the racemic mixture, and then the pharmacologically more active isomer is introduced as a patent-extender, usually with recommended doses that are half of those of the racemate.
Thanks undopaminergic for your reply but that was exactly what I was getting at. I don't understand a single sentence on that link, I've looked at it before.Put it this way, is it like citalopram v's escitalopram. I know citalopram is weaker in concentration because it's slightly different. Which is the weaker between modafinil and armodafinil?
You're obviously well read/educated in chemistry and I'm not, could you explain it in a different way? The shiny objects caught my attention again and it was all too much to take in, or are you telling me that modafinil is the patent extender, which I do understand because that would explain the price.
Thanks C
Posted by Larry Hoover on May 10, 2008, at 20:39:05
In reply to Re: modafinil and armodafinil, how do they differ? » undopaminergic, posted by cactus on May 10, 2008, at 19:33:31
> Put it this way, is it like citalopram v's escitalopram. I know citalopram is weaker in concentration because it's slightly different.
It's better said that citalopram is the combination of two almost identical molecules, only one of which is active. The two forms are arbitrarily (according to set rules, mind) called R- and S- structures, simply to differentiate them. We've discovered that the S- form of citalopram is the active one, and the R- form can be thought of as diluting the active form. There's more to it, but that's the gist.
Consider someone with only one hand. They might have to buy pairs of gloves to get the one that they need. The other is of no use. When chemists synthesize molecules, random events occur that make R- and S- structures form. To use the glove analogy, we know how to synthesize gloves, but we have an equal chance of making left (S) and right (R) gloves. With a little extra work, we can separate them, and that's what's done with drugs like escitalopram being isolated from the blended citalopram, and armodafanil, which is isolated from the mixture of R-modafanil and S-modafanil that is sold as Modafanil.
> Which is the weaker between modafinil and armodafinil?
Modafanil is 'weaker', or at least, less specific. S-modafanil might do different things than R-modafanil, as opposed to simply being inactive. But modafanil is the weaker drug.
> You're obviously well read/educated in chemistry and I'm not, could you explain it in a different way? The shiny objects caught my attention again and it was all too much to take in, or are you telling me that modafinil is the patent extender, which I do understand because that would explain the price.
>
> Thanks CArmodafanil is the patent extender, as it will be protected until the year 2023.
Lar
Posted by cactus on May 10, 2008, at 22:08:30
In reply to Re: modafinil and armodafinil, how do they differ? » cactus, posted by Larry Hoover on May 10, 2008, at 20:39:05
Thanks Lar, I just know what does and doesn't work for me. Right now it's modafinil. So thanks for explaining it to me. I'm not a very scientific minded person.
I do research all the meds I have taken, like patient info sheets, and as much data/research I can find online and comprehend, as to how it's working for me (or supposed to be), and then I get lost with the intimate chemistry details and make up structures pertaining to the dynamics/mechanics of it all.
Thanks again C
Posted by undopaminergic on May 11, 2008, at 11:42:20
In reply to Re: modafinil and armodafinil, how do they differ? » Larry Hoover, posted by cactus on May 10, 2008, at 22:08:30
It may be worth emphasising that if you're using modafinil, then you're using armodafinil, because modafinil is a mixture of one part armodafinil, and one part of its mirror image, S-modafinil.
Posted by SLS on May 11, 2008, at 12:28:07
In reply to Re: modafinil and armodafinil, how do they differ?, posted by undopaminergic on May 11, 2008, at 11:42:20
> It may be worth emphasising that if you're using modafinil, then you're using armodafinil, because modafinil is a mixture of one part armodafinil, and one part of its mirror image, S-modafinil.
It is interesting, though, that the clinical properties of Lexapro differ from that of Celexa. Lexapro tends to be more stimulating (except at the two-week mark, where it can produce transient fatigue). Some people respond robustly to one and not the other. There was some conjecture that the the r-isomer actually interferes with some of the clinical benefit from the s-isomer.
- Scott
Posted by Larry Hoover on May 11, 2008, at 14:22:22
In reply to Re: modafinil and armodafinil, how do they differ?, posted by SLS on May 11, 2008, at 12:28:07
> > It may be worth emphasising that if you're using modafinil, then you're using armodafinil, because modafinil is a mixture of one part armodafinil, and one part of its mirror image, S-modafinil.
>
> It is interesting, though, that the clinical properties of Lexapro differ from that of Celexa. Lexapro tends to be more stimulating (except at the two-week mark, where it can produce transient fatigue). Some people respond robustly to one and not the other. There was some conjecture that the the r-isomer actually interferes with some of the clinical benefit from the s-isomer.
>
>
> - ScottIt's more than conjecture. R-citalopram is a serotonin reuptake inhibitor inhibitor. It modifies the conformation of the receptor complex by binding at a site other than the active site. The effect is most dramatic in those with one specific serotonin transporter gene allele.
Lar
Posted by SLS on May 11, 2008, at 15:34:04
In reply to Re: modafinil and armodafinil, how do they differ? » SLS, posted by Larry Hoover on May 11, 2008, at 14:22:22
Thanks, Larry. I hadn't been aware of these findings. It's nice when some association can be seen between the pure research and the clinical observation. It makes me think that we are not as blind to the inner workings of the black box than we were only a decade ago.
- Scott
****************************************************> > > It may be worth emphasising that if you're using modafinil, then you're using armodafinil, because modafinil is a mixture of one part armodafinil, and one part of its mirror image, S-modafinil.
> >
> > It is interesting, though, that the clinical properties of Lexapro differ from that of Celexa. Lexapro tends to be more stimulating (except at the two-week mark, where it can produce transient fatigue). Some people respond robustly to one and not the other. There was some conjecture that the the r-isomer actually interferes with some of the clinical benefit from the s-isomer.
> It's more than conjecture. R-citalopram is a serotonin reuptake inhibitor inhibitor. It modifies the conformation of the receptor complex by binding at a site other than the active site. The effect is most dramatic in those with one specific serotonin transporter gene allele.
Posted by Larry Hoover on May 11, 2008, at 19:45:02
In reply to Re: modafinil and armodafinil, how do they differ?, posted by SLS on May 11, 2008, at 15:34:04
> Thanks, Larry.
You're welcome. I'll be posting my thoughts on your depression/Alzheimer's thread soon.
> I hadn't been aware of these findings. It's nice when some association can be seen between the pure research and the clinical observation.
I also think that the cynical view of "patent extension" may be a low blow when applied without studying the individual case.
> It makes me think that we are not as blind to the inner workings of the black box than we were only a decade ago.
It's still a pretty dark box, if not pure black. But, yes, I'm hopeful that we'll continue to make advances. Certain of it, in fact.
Here are some references for the effects of R-citalopram on S-citalopram binding....
http://www.ncbi.nlm.nih.gov/pubmed/16448580
Shows that R-citalopram reduces s-citalopram binding to SERT (the serotonin transporter).
http://www.ncbi.nlm.nih.gov/pubmed/17235610
Shows that equivalent doses of S-citalopram provided by Lexapro and Celexa produce similar blood concentrations, but significantly reduced SERT binding with Celexa, demonstrating the reduced efficacy of the racemic mixture.
In other words, 10 mg of Lexapro is more effective than 20 mg of Celexa, even though they contain identical amounts of the active principle.
Lar
Posted by Larry Hoover on May 11, 2008, at 20:05:48
In reply to Re: modafinil and armodafinil, how do they differ? » Larry Hoover, posted by cactus on May 10, 2008, at 22:08:30
> Thanks Lar, I just know what does and doesn't work for me. Right now it's modafinil. So thanks for explaining it to me. I'm not a very scientific minded person.
>
> I do research all the meds I have taken, like patient info sheets, and as much data/research I can find online and comprehend, as to how it's working for me (or supposed to be), and then I get lost with the intimate chemistry details and make up structures pertaining to the dynamics/mechanics of it all.
>
> Thanks again CI do appreciate the difficulty in grasping these concepts. If you'll permit me to expound a little more.....
If you consider nuts and bolts, or wood screws, as an example....by convention, we've adopted a universal system of thread pitch that tightens when turned clockwise, and loosens when turned anti-clockwise. The aphorism for that is "righty-tighty, lefty-loosy". It could have been the other way around, but we only have the one pattern. Mother nature is like that, too.
All common amino acids have a left-handed twist. We call them L-amino acids. If you come across a DL designation (e.g. D,L-phenylalanine, or DLPA), it means that they're synthetic. Mother nature uses enzymes that can only create L-molecules, but man uses cruder methods that make both in equal amounts. Using that wood screw analogy, it would be as if we made screws that tightened (or loosened) with either a left or a right twist. Grossly inefficient, wot? Moreover, if you came upon a wood screw in a wooden article, you'd have no way to determine which way to turn it to loosen it, as the threads are hidden from view. That sort of thing just wouldn't survive in Nature, and long ago, the L-twist became the only game in town.
Drugs that we make are also sensitive to the same "twist" issue, because only one of the twists matches up with the natural twist of the target tissue. The ones with the wrong twist sometimes just gum things up, even though we hope they're simply inactive.
I haven't studied the modafanil "twist" issue, but I'd not be too surprised to discover that there may be a good reason to separate the active form (in this case, armodafanil, or R-modafanil) from the S-modafanil. Whether that is worth a new patent.....<shrug> If nothing else, if modafanil goes off-patent, it will likely be available at much better pricing as a generic. It may or may not be worth paying a substantial premium to get the armodafanil.
Lar
Posted by Ron Hill on May 11, 2008, at 23:23:03
In reply to Re: modafinil and armodafinil, how do they differ? » cactus, posted by Larry Hoover on May 10, 2008, at 20:39:05
Posted by cactus on May 12, 2008, at 3:46:15
In reply to Re: modafinil and armodafinil, how do they differ? » cactus, posted by Larry Hoover on May 11, 2008, at 20:05:48
Posted by Molybdenum on May 15, 2008, at 18:55:11
In reply to Re: modafinil and armodafinil, how do they differ? » cactus, posted by Larry Hoover on May 11, 2008, at 20:05:48
Dear Larry,
Since I've read your very interesting posts, I came across the following article. I'm not convinced the author is completely sane, but it's got me thinking about some matters related to the content and I'd very much love to hear your opinions.
http://www.wipo.int/pctdb/en/wo.jsp?IA=WO2007013962&DISPLAY=DESC
So basically, the author believes that the "d-modafinil" (dextrorotatory enantiomer) and "1-modafinil" (levorotatory enantiomer) have active yet differing half lives. I can't understand why s/he thinks that idea is patentable, but that's not my query.
I know that the name brand modafinil (Profigil, Modavigil here) is said to me racemic. As it's too expensive for me, I have been buying it from India & Bosnia. My question then is: is it possible that a modern factory that is trying to cut costs to compete in the generic market, could in fact be accidentally producing a non-racemic modafinil? If they are trying to cut corners here & there, could they unintentionally produce modafinil that contained differing proportions of the D and 1 enantiomers?
Or is there basically only one way to make modafinil & it just so happens that it always turns out racemic?
Your in humble respectedness :)
Molly Be Damned.
This is the end of the thread.
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