![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by winter on July 23, 2002, at 19:39:11
3 Beers Effect,
I have been searching through nearly every relavent post for the last year looking for useful information regarding side effects of Dexedrine. As so far the most useful information has come from none other than yourself. However, all the information I have found has been indirectly realted to my question and I have not been able to find enough information to piece together to answer it myself. Thus I have decided to just ask you and hope that you will respond to me in a timely fashion. I am asking you directly as I have noticed that you semm to have a pletheroa of information at hand that has originated from extensive reasearch.The side effects that I am concerned with have been albeit typical side effects. Nausea, Light headedness, dizzyness, headache,feeling like one cannot breathe, cramps in the arms and legs as wells as through the chest and randomly elsewhere, Feeling of vague numbness in hands and feet. These occur not all at once but in various combinations. They also occur in "waves". You are fine for a while then a side effect wave comes on for any where for 10-45 minutes. Negligble in the morning, begin being noticible in afternoon and become progressivly worse into the night. There isn't anything critically wrong with me. After this had been happening for two days I got fed up and went to the ER. Nothing wrong. Anxiety or medication reaction they say.
Here is some more background. I have been taking Dexedrine end of May. Began having side effects on the 18 of July. List of meds:
Dexedrine: 10 mg Span 10mg reg AM 10 mg reg PM
(since friday decided to decrease dose;10span5reg AM 7.5mgPM, Tuesday 10span5reg AM 5mgPM)
Topamax:75mg AM
Superlowdose BirthControlPils: AM
Zyrtec:10mg(stopped taking 3wks ago)
Allegra: 180mg(took for 4 days, few days after stopped started feeling bad, suspicion might be associated with side effects; ie allergic reaction to allegra)Health in general: Sex F Height 5'5 Weight 183
BMI:46(awful) Blood Pressure before and after Dex:110/72 Pulse:92(too high, i think)Reason for taking Dexedrine; Idiopathic hypersomnia and ADD. Topamax=Migraines. Antihistimines=urticaria.
There is a background for you to hopefully elimnate the need to back and forth questions and answers.
Now to get to my point; In a post from June 5, 2002 Originally entitled "Pricing of Ritialin Dexedrine and Adderal, Whats up?" You replyed to a post by nightlight. In your post you spoke of peripheral side effects and which different forms of Dexedrine and other stimulants were more likely to cause these according to the literature.
Once upon a time I was highly inteligent then I became severly depressed and in those years I think my brain rotted. Also though the Dexedrine genrally helps with the hypersomnia is only occasionally helps with the ADD. Today is not one of those days. I very much want to fully understand what you were trying to get across because I know it has some relavance to my situation. I need to revaulate my dosage and I feel that this information you have provided will be of use to me as well as information that I have read in others posts regarding blood levels and coparisons between the various stimulants. Perhaps you could expand on this post for maand clean it up a little and explain some terms such as "isomer". Thank you.
I know everyone is different and we all have unique chemistrys and will react to meds differently. However your research and knowledge can give me some starting ground and perhaps help circumvent all the trial and error whilst trying to eliminate these side effects I am feeling. So anything you know about how the dexedrine and all its various forms work(I am not eager to try a differnt stimulant yet) that might help myself and my doctor figure out the correct dosage would be quite helpful. Thank you.If you are wondering, since I have lowered the dose of the reg Dex pills I haven't noticed a signifigant improvement. My instincts are telling me that two spans a day will be better since in the after noon when I take just the reg is when I begin to feel lousy. Initially I began taking just a span in the morn and I had mini crashes at three and then I would fall asleep at 7 so I need a second dose.
Thank you.
Posted by Jerrympls on July 23, 2002, at 21:03:48
In reply to 3Beers Effect-Question for you on Dexedrine, posted by winter on July 23, 2002, at 19:39:11
Not that you asked me, but I thought I may tell you of some of my experiences -which may or maynot help. I have been taking Dexedrine for many months now and although it doesn't work as well as it has in past years, it still helps. Anyway, what I noticed while reading your post was many of the "weird" side effects you listed were almost exactly the same as the ones I experienced when adding Topamax to the Dexedrine. tingling in the hands and feet, feeling "dumb" - can't remember common words while mid sentence although I could "see" them in my head, lightheadedness, dizziness, and a terrible "burning tongue" effect - especially when i drank carbonated drinks, etc. I was up to 400mg of Topamax and 60mg of Dexedrine along with some other meds including Zyrtec. I had no posiitve effects from the Topamax and all side effects vanished as I stopped taking it. Now, I'm not saying it's the Topamax that's making you feel like crap - I'm just relating my experiences. I hope you figure it out......
Jerry
Posted by BekkaH on July 23, 2002, at 22:30:20
In reply to 3Beers Effect-Question for you on Dexedrine, posted by winter on July 23, 2002, at 19:39:11
Hi Winter,
I haven't seen Mr. 3 Beers here in a few weeks. I would like to mention that some doctors refer to Topamax as "Dopamax." Of all the anticonvulsants, it is the one that causes the worst cognitive impairment. Now, perhaps you must take it and have no alternative, but I just think you should know that Topamax is notorious for causing brain fog, so don't blame yourself, your depression or Dexedrine.
Let's hope 3 Beers returns soon.
Bekka
Posted by Xevious on July 25, 2002, at 0:11:40
In reply to 3Beers Effect-Question for you on Dexedrine, posted by winter on July 23, 2002, at 19:39:11
I'll tackle a few more questions while we all wait for 3beers...
First, for a fairly simplified explanation of the more technical stuff: Many organic molecules come in two "flavors" called optical isomers, or enantiomers. Although the atomic arrangement of both enantiomers is identical (same chemical formula), the three-dimensional structural arrangement of one enantiomer mirrors that of the other. Because enantiomers rotate polarized light, they are also called "optical isomers;" the enantiomer that rotates polarized light to the right is called "dextrorotary" or "d," the enantiomer that rotates polarized light to the left is called "levorotary" or "l".
Why is this important? Well, if you have your GREs coming up soon, then you know the answer to that question! ;) But seriously, the really important concept here for us is that enzymes, which are the building blocks of our metabolism, are so selective that they usually can only use one of the two optical isomers. This is why, for example, 5-hydroxytryptophan suppliments usually are purified to contain only the levorotary (5-hydroxy-l-tryptophan) enantiomer - the dextrorotary enantiomer cannot be metabolised and is therefore ineffective.
With the psychostimulants, the situation is a bit more complicated - the dextrorotary enantiomer is said to have more of a central nervous system (CNS) stimulating effect, whereas the levorotary enantiomer is said to have more of a peripheral nervous system (PNS) stimulating effect.
*Dextro*amphetamine (Dexedrine) and the newer form of methylphenidate (Ritalin) called Focalin, which is exclusively d-methylphenidate, contain only d enantiomers. (Focalin is designed to (hopefully) eliminate many of the side-effects of plain old ritalin, which is a mixture of equal parts d and l enantiomers.) Clear as mud?
Okay. So Dexedrine and Focalin are exclusively d, Ritalin and Concerta (which are the same stuff, only concerta comes in very high-tech time-release packaging) are a mixture of d and l, and Adderall is equal parts dextroamphetamine saccharate, dextroamphetamine sulfate, amphetamine aspartate, and amphetamine sulfate, which means that it is approximately 75% d and 25% l.
Please note that Adderall DOES NOT contain any methylphenidate (Ritalin), as has been mentioned here several times before. Also note that my previous comment about the CNS/PNS stimulation effects of d and l isomers is very subjective and not, to my knowledge, a scientifically proven fact. As you pointed out, each individual's chemistry is different. Adderall tends to be preferred by the majority of ADHD folks, though my subjective opinion is that non-hyperactive folks like myself are underrepresented in such studies.
I've tried Ritalin, Adderall, and Dexedrine now, and Adderall is my favorite of the lot. I also suffer from hypersomnia and chronic sleepiness, and am anxious (well, only on Dexedrine!) ;) to give Provigil a try. Here's my qualitative experiences with the pstims:
Ritalin: almost no positive effects, caused "amping up," mild anxiety and general feelings of ickyness. The speed with which it hit and left my system made me feel like I had gone a round or two in the ring with a heavyweight champion.
Adderall: great effects on everything but wakefulness and hypersomnia, so it helped my ADD but I was still falling asleep in class! Side effects were mild anxiety, elevated heart rate and blood pressure.
Dexedrine: didn't touch the hypersomnia at all, but felt much better than Adderall, except for the really nasty side effects, which included TMJ-type symptoms (jaw tension, misalignment, and discomfort), feeling completely "washed out" at the end of the day, and once again, a lot of hard-to-explain general ickyness.
Provigil is a CNS stimulant that promotes wakefulness and is currently FDA approved for the treatment of narcolepsy, but several studies (look at www.biopsychiatry.org or search medline, publist or infotrieve) have shown it to have an excellent effect on ADD, as some of the members here will attest. Because its primary action is on wakefulness, I'm trying it next. Studies (again, check same sources - sorry, I don't have real references) have shown that Provigil + Dexedrine can coexist without additional toxicity, but I haven't found a similar study on Provigil + Adderall.
Good luck! I hope I've answered some of your questions without overwhelming you with too much babble! ;)
-Xevious
Posted by BekkaH on July 25, 2002, at 5:54:40
In reply to Re: 3Beers Effect-Question for you on Dexedrine, posted by Xevious on July 25, 2002, at 0:11:40
Also note that my previous comment about the CNS/PNS stimulation effects of d and l isomers is very subjective and not, to my knowledge, a scientifically proven fact. As you pointed out, each individual's chemistry is different. Adderall tends to be preferred by the majority of ADHD folks, though my subjective opinion is that non-hyperactive folks like myself are underrepresented in such studies.
>
************************************************
Xevious,
Are you sure that the CNS/PNS stimulation issue of the d and l isomers is only subjective and not scientifically proven? I've read about this in so many places, including some psychopharmacology texts, so I'm wondering whether it is just subjective.As far as Adderall being preferred by the majority of ADHD folks, I think one reason for that is that it has been so aggressively marketed in recent years. Adderall is the exact same chemical composition as a drug called Obetrol that is no longer available. Apparently it was a diet drug. Shire Pharmaceuticals bought the rights to the drug, renamed it, and aggressively packaged it for the ADHD market. The name "Adderall" has much less of a stigma attached to it than the name "amphetamine," "Dexedrine," or any of the previously available formulations (such as the above-mentioned Obetrol). By the way, my psychopharmacologist believes that of all the psychostimulants, Dexedrine is most effective for depression.
Posted by Xevious on July 25, 2002, at 12:43:14
In reply to Question for you - Xevious, posted by BekkaH on July 25, 2002, at 5:54:40
I completely agree; I think that marketing has had much to do with this issue, especially since re-labeling Obetrol allowed Shire to re-patent it, while the patent on Dexedrine (also Shire, IIRC) is long since expired. The stigma also plays a role; even though Obetrol was abused about as much as Dexedrine in years past, Adderall has given it a shiny new name.
All that said, I've been unable to find any studies confirming the d/l CNS/PNS connection. If anyone here has links or references, I'd really appreciate it if you'd post them here! I very much believe that the d and l enantiomers affect folks differently, and the anecdotal evidence I've heard and read seems to indicate that the d form is more CNS selective, but I'm not completely sold on the CNS/PNS split being so cut and dried. In my personal experience, psychopharmaceutical action rarely ever is! :)
But that's what happens when you take a shotgun approach to "fixing" such an enormously complex biochemical machine like the brain...
Another reason why Adderall is the preferred ADHD med is probably because it is 25% l enantiomer - a little nudge of PNS stimulation can really wake you up, assuming that you can tolerate the side effects. Personally, this is why I want to give Provigil a try. Theoretically, it gives more wakefulness for less side effects. (Crossing fingers, praying to the god of pharmaceuticals...)
Obviously, there is either some real scientific evidence out there (or just incredibly strong anecdotal evidence!) in favor of the d enantiomer of methylphenidate, or Focalin wouldn't have been developed.
Thanks for checking me, I do appreciate it! I'm still sorting out facts from assumptions on all of this stuff, and it's just a bit confusing! ;)
-Xevious
> >
> ************************************************
> Xevious,
> Are you sure that the CNS/PNS stimulation issue of the d and l isomers is only subjective and not scientifically proven? I've read about this in so many places, including some psychopharmacology texts, so I'm wondering whether it is just subjective.
>
> As far as Adderall being preferred by the majority of ADHD folks, I think one reason for that is that it has been so aggressively marketed in recent years. Adderall is the exact same chemical composition as a drug called Obetrol that is no longer available. Apparently it was a diet drug. Shire Pharmaceuticals bought the rights to the drug, renamed it, and aggressively packaged it for the ADHD market. The name "Adderall" has much less of a stigma attached to it than the name "amphetamine," "Dexedrine," or any of the previously available formulations (such as the above-mentioned Obetrol). By the way, my psychopharmacologist believes that of all the psychostimulants, Dexedrine is most effective for depression.
>
Posted by winter on July 25, 2002, at 23:43:47
In reply to Re: Question for you - Xevious, posted by Xevious on July 25, 2002, at 12:43:14
Thank you all for the information.
On the note of Provigil. I have taken it and it did not affect me what so ever. For the Hypersomnia it did not wake me up, keep me alert, or anything along those lines all it did was maintain a "non-asleep" like state. I would be exhausted both physically and mentally dying to fall asleep but not easily able to. If I went and lay down in a dark room I could, however I would not be able to fall asleep sitting in a car or lounging in a chair like I normally could when I was not taking the Provigil. For the ADD which is fairly mild it also did nothing. All in all I did not like the Provigil as it gave me the feeling as if I had stayed up for the past few days and was just running on sleep deprivation and caffine.
(though without the jitters and what not).Provigil was very foggy for me.Jerrympls-
you mentioned the Topamax. I am glad you did. Thank you. I don't think Topamax is the issue as I have been taking it for two years now and I have never had a problem with it. The only problem I have had is the same burning sensation you mentioned with carbonated drinks! I found this to be a blessing in disguise. I drank far to much soda before I began the Topamax and now I am unable to touch the stuff! I remember about a week after I had been taking the Topamax I was at a restaurant with my boyfriend and I ordered a coke and I kept sending it back thinking it was flat. I soon started experiencing the burning feeling whilst drinking as well. Strangest thing first it tastes like its been sitting out in the desert sun (still as can be) for weeks and then the drink burns like hell! Sometimes my boyfriend has a rootbeer and I can smell it(Oh it smells really good!) So I will taste it anyway, just because and just incase the burning has gone away. It never does. The drinks always taste bad and hurt. Severly limits your beverage choices. I am excited to hear that you experienced this as well. My neurologist had never heard of anyone have this sort of reaction. I am happy to know I am not the only one.Sorry about the digression. Thank you all for you input.
My psychopharm and I decided for me to try Klonopin. Since most of this is most likely anxiety related. I have a tendancy to notice eveything that goes on in my body. One ache and I notice more thus begins a vicious cycle. The mind can be very powerful. After I get used to the Klonopin begins more dosage adjustment.
Here is a thought womens hormones are constantly fluctuating, thus affecting their entire bodies. How do you think this affects the various stimulants such as Adderal, Ritialin, Concerta, Dexedrine, etc... You know them all.
I have my own thoughts. Just thought this might be a contributing factor.
Posted by Iago Camboa on July 26, 2002, at 5:00:38
In reply to Question for you - Xevious, posted by BekkaH on July 25, 2002, at 5:54:40
> Xevious,
> Are you sure that the CNS/PNS stimulation issue of the d and l isomers is only subjective and not scientifically proven? I've read about this in so many places, including some psychopharmacology texts, so I'm wondering whether it is just subjective.Hi Bekka,
Of course it is you (and all the world with you) who is right about the ACTUAL (OBJECTIVE) differences between the properties of Dexedrine (= d-amphetamine, the 'good' enantiomer) and the l-amphetamine, as is the rule with 99.99% of substances that happen to appear in both l- & d- varieties: the rarer in nature is the two being equally active. And there is NO such thing as people (whose body) 'prefer' the -l variety and people who 'prefer' the -d (that would mean different genetic material (not less!!) and would be impossible for any two individuals of our species).
It is an absurdity, as impossible as one person whose body had one certain aminoacid of the d-variety instead of the actual one (of the l-variety); that person could not even eat terrestrial food as all life on earth is based on the exact same aminoacids (mainly of the l-variety) and our enzymes are encoded genetically and built that way that they are only able to deal with one and only one of the two (theoretical) possible enantiomers: just the one that happens to appear naturally in our planet. It is the nature of things, as sure as all electrons being negative and protons positive.
There is no need to 'prove' scientifically that d-amph is much more active and is more CNS oriented & l-amph is more PNS oriented: it is a simple fact of life, one compound happens to have the properties such & such and the other some other properties. In my opinion our friend Xevious is an intelligent guy but has yet to learn many things (as we all have) and get a little more 'common sense' before he can post 100% reliably to his own self-enjoyment and the benefit of all PB community.Kind regards,
Iago
Posted by Xevious on July 28, 2002, at 1:23:59
In reply to Re: Question for you - Xevious » BekkaH, posted by Iago Camboa on July 26, 2002, at 5:00:38
Iago (and others),
Yes, I certainly have much to learn! That's one of the reasons why I'm here, and when I'm speculating, I'm careful to point out as much. However, had you read my post more carefully, you would have observed that I at no point suggested that different people manufacture custom enzymes that "prefer" different enantiomers; I did, however, question the assumption that has been posted here many times before that the d enantiomer of amphetamines (or pstims in general) has high CNS selectivity whereas the l enantiomer has high PNS selectivity. For this assumption, I have found zero evidence outside of a few anecdotal reports made by posters on this site.
From my (albeit limited) knowledge of organic chemistry, in the simplest case, the d enantiomer would simply be metabolised more effectively than the l enantiomer, which would not support the CNS/PNS selectivity assumption. In a more complex case, alternate metabolic pathway(s) would create a metabolite that is PNS selective. In this latter case, the degree of d-vs.-l selectivity evidenced by each metabolic pathway could account for d/l CNS/PNS selectivity. In either case, there is a specific biochemical mechanism responsible for the process of x-amphetamine -> CNS stimulation and/or x-amphetamine -> PNS stimulation.
Here are the facts that I *am* aware of:
d-amphetamine is the more active enantiomer; however, l-amphetamine is also a biochemically active enantiomer. There are several pathways available for the metabolism of amphetamine, including hydroxylation and deamination, each resulting in different intermediate compounds. I do not know if d-amphetamine is the eutomer for each of these pathways. The presence of multiple pathways is responsible, in part, for the fact that different people respond differently to a similar dose of any given compound.
As a scientist, I certainly contend with the idea that one can satisfactorily explain *any* process by repeating a mantra of "it's just a fact of life." If, for example, the medical field took this stance, then we would have no medicines as illness would merely be a "fact of life."
My question to you, Iago, since you have asserted your knowledge in the subject of organic chemistry, is this: if d-amphetamine is indeed more CNS-oriented and l-amphetamine more PNS-oriented, why? Which amphetamine metabolite is responsible for exclusively stimulating the central nervous system while leaving the peripheral nervous system untouched? I ask this question honestly, as I did in my original post, and would appreciate an answer intended to decrease my ignorance as opposed to triumphantly pointing it out to the rest of the world.
Educate me.
-Xevious
> > Xevious,
> > Are you sure that the CNS/PNS stimulation issue of the d and l isomers is only subjective and not scientifically proven? I've read about this in so many places, including some psychopharmacology texts, so I'm wondering whether it is just subjective.
>
> Hi Bekka,
>
> Of course it is you (and all the world with you) who is right about the ACTUAL (OBJECTIVE) differences between the properties of Dexedrine (= d-amphetamine, the 'good' enantiomer) and the l-amphetamine, as is the rule with 99.99% of substances that happen to appear in both l- & d- varieties: the rarer in nature is the two being equally active. And there is NO such thing as people (whose body) 'prefer' the -l variety and people who 'prefer' the -d (that would mean different genetic material (not less!!) and would be impossible for any two individuals of our species).
> It is an absurdity, as impossible as one person whose body had one certain aminoacid of the d-variety instead of the actual one (of the l-variety); that person could not even eat terrestrial food as all life on earth is based on the exact same aminoacids (mainly of the l-variety) and our enzymes are encoded genetically and built that way that they are only able to deal with one and only one of the two (theoretical) possible enantiomers: just the one that happens to appear naturally in our planet. It is the nature of things, as sure as all electrons being negative and protons positive.
> There is no need to 'prove' scientifically that d-amph is much more active and is more CNS oriented & l-amph is more PNS oriented: it is a simple fact of life, one compound happens to have the properties such & such and the other some other properties. In my opinion our friend Xevious is an intelligent guy but has yet to learn many things (as we all have) and get a little more 'common sense' before he can post 100% reliably to his own self-enjoyment and the benefit of all PB community.
>
> Kind regards,
> Iago
>
>
Posted by Iago Camboa on July 29, 2002, at 7:11:48
In reply to Re: Question for you - Xevious, posted by Xevious on July 28, 2002, at 1:23:59
Xevious,
Oh heaven. You look to me like that person who began to criticize all modern Biology textbooks on the grounds that they fail to describe and have in no account three most 'important animals', namely the chimaera, the unicorn and the sphinx. What has one to respond? Perhaps something like this: 'those creatures are never mentioned probably because they don't exist or at least were never described by any biologist; if you feel uncomfortable with that fact try to find one instance of each and describe them in an appropriate publication yourself: perhaps then they find acceptance in science; go ahead and good luck! This I mention without any intention of ridiculing you but to make an important point: in science the 'onus probandi', i.e. the burden of proof is on the ONE WHO AFFIRMS some provocative statement. There is no need for anybody to bother to prove that those hypothetic animals cannot exist, the silence is response enough...
In our case, for anybody who wants to know the truth it is enough to get to a search engin and type the single word 'dextroamphetamine' and hit the enter key: they will find a tremendous wealth of information as is appropriate for one of the most important & useful psychotropic substances ever discovered by man. One will find monografies about the tremendously important medicine 'Dexedrine' (or rather 'dexedrine', as the word came to be felt as a common noun, shorthand for the longer name 'dextroamphetamine'), an indispensable medicine in our world. Now type at the search engin's prompt the word 'levoamphetamine' and press 'enter' again. You will find nothing interesting: there is no medicine based on that chemical compound, for the good reason that it is an useless substance to anyone: if you are interested in its CNS effects, dexedrine is a substance a number of times stronger and devoid of its side effects (due to its unwanted action on the PNS).
Anybody who wants to can get ANY treatise on psychopharmacology and take a look on the chapter where pstims are dealt with: they will find that 'l-amphetamine' is a 'non-entity', compared to the all-importance of its twin (d-amphetamine). I said and repeat it here again: it is a fact of life without appeal that only d-amph is relevant and l-amph is useless. (l-amph was born under an unlucky star, if you prefer things put that way...). And if you feel unhappy with the actual situation go ahead and publish in an appropriate place your ideas about the excellence of l-amph and we will all see the results. Good luck and be happy in your endeavor! Maybe you can convince a drug manufacturer and they put a new medicine into the market, perhaps 'Levedrine' or the like...
About your 'biochemical' reasonings, I'm sorry but they mean to me as much as nothing: they seem to me a cloud of dust thrown to the eyes of fools and simpletons (though I'm by no means an expert either on organic chemistry or on biochemistry or on (psycho-)pharmacology), without any sound contents.
And just take this extra ado. It is also COMMON established knowledge (facts of life without appeal) that alcohol is a depressant of the CNS and caffeine a stimulant thereof. Does it make sense beginning to assert the nonsense that there exist no prove to that effect and then claim and defy other people to explain WHY is alcohol a depressant and caffeine a stimulant? Is that a honest request? I'm afraid you need more than learning your organic chemistry, your biochemistry and your psychopharmacology: you need also learn about intellectual honesty and civil manners...Have a good day.
Iago
> Iago (and others),
>
> Yes, I certainly have much to learn! That's one of the reasons why I'm here, and when I'm speculating, I'm careful to point out as much. However, had you read my post more carefully, you would have observed that I at no point suggested that different people manufacture custom enzymes that "prefer" different enantiomers; I did, however, question the assumption that has been posted here many times before that the d enantiomer of amphetamines (or pstims in general) has high CNS selectivity whereas the l enantiomer has high PNS selectivity. For this assumption, I have found zero evidence outside of a few anecdotal reports made by posters on this site.
>
> From my (albeit limited) knowledge of organic chemistry, in the simplest case, the d enantiomer would simply be metabolised more effectively than the l enantiomer, which would not support the CNS/PNS selectivity assumption. In a more complex case, alternate metabolic pathway(s) would create a metabolite that is PNS selective. In this latter case, the degree of d-vs.-l selectivity evidenced by each metabolic pathway could account for d/l CNS/PNS selectivity. In either case, there is a specific biochemical mechanism responsible for the process of x-amphetamine -> CNS stimulation and/or x-amphetamine -> PNS stimulation.
>
> Here are the facts that I *am* aware of:
>
> d-amphetamine is the more active enantiomer; however, l-amphetamine is also a biochemically active enantiomer. There are several pathways available for the metabolism of amphetamine, including hydroxylation and deamination, each resulting in different intermediate compounds. I do not know if d-amphetamine is the eutomer for each of these pathways. The presence of multiple pathways is responsible, in part, for the fact that different people respond differently to a similar dose of any given compound.
>
> As a scientist, I certainly contend with the idea that one can satisfactorily explain *any* process by repeating a mantra of "it's just a fact of life." If, for example, the medical field took this stance, then we would have no medicines as illness would merely be a "fact of life."
>
> My question to you, Iago, since you have asserted your knowledge in the subject of organic chemistry, is this: if d-amphetamine is indeed more CNS-oriented and l-amphetamine more PNS-oriented, why? Which amphetamine metabolite is responsible for exclusively stimulating the central nervous system while leaving the peripheral nervous system untouched? I ask this question honestly, as I did in my original post, and would appreciate an answer intended to decrease my ignorance as opposed to triumphantly pointing it out to the rest of the world.
>
> Educate me.
>
> -Xevious
>
>
Posted by Xevious on July 29, 2002, at 18:06:32
In reply to Re: Question for you - Xevious, posted by Iago Camboa on July 29, 2002, at 7:11:48
I'll just very simply re-state the opinions/questions/assumptions that I made originally, since there has certainly been some misunderstanding.
DEXTROamphetamine is the active enantiomer of amphetamine. That means it works anywhere from a little to a whole heck of a lot better than levoamphetamine, depending on enzyme selectivity. In the case of this chemical, biological selectivity for the d form is high. THEREFORE, dextroamphetamine is going to be a lot more effective, gram for gram, than levoamphetamine. Simple, and lots of hard science to back it up so we know that it isn't something like placebo effect. I never questioned this, and while Iago's rant on the efficacy of dextroamphetamine versus chimeramphetamine was certainly entertaining, it wasn't very illuminating.
MY QUESTION was over the claim which has been made here numerous times that LEVOamphetamine is a PNS stimulant, rather than merely being less effective than dextroamphetamine or a biochemically inert substance. It was this assumption that I was contesting, as I've found zero evidence to back it up.
Anyone else have anything useful to contribute? :)
-Xevious
Posted by Seamus2 on July 29, 2002, at 20:30:48
In reply to Re: Question for you - Xevious, posted by Xevious on July 29, 2002, at 18:06:32
From Goodman and Gilman's 1st ed. 11th printing pg 436
Benzedrine exists in three forms due to the presence of an asymmetric carbom atom, the d-, l- and dl-benzedrines. The dextrorotary form appears to be from two to four times more active than the other two isomers, as determined by clinical tests in normal individuals and in patients with nacrolepsy, postencephalitic Parkinson's disease and postural hypotension (Prinzmetal and Alles, 1939). The order of decreasing potency is as follows: d-benzedrine, racemic benzedrine, l-benzedrine. This is particularly interesting because in most instances, levorotary compounds possess considerably more pharmacodynamic activity than the dextro or racemic isomers.
If you have a wayback machine handy, you could check:
3. Alles G.A.: The comparative physiological actions of dl- -phenylisopropylamines. I. Pressor effects and toxicity. J. Pharmacol. Exp. Ther., 1933, 37, 339-354.
4. Alles G.A., Prinzmetal M.: The comparative physiological actions of dl--phenylisopropylamines. II. Bronchial effects. J. Pharmacol. Exp. Ther., 1933, 38, 161-174.Seamus
Posted by Iago Camboa on July 30, 2002, at 4:01:21
In reply to Re: Question for you - Xevious, posted by Seamus2 on July 29, 2002, at 20:30:48
This is the end of the thread.
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