l-amphetamine salts: Why its still added to pharms

[Smyth]

Separating the isomers of amphetamine or otherwise conducting an enantioselective synth thereof, while difficult for a garage chemist would be a complete doddle in an industrial strength laboratory. Any amphetamine salts chosen in a prescription med is done deliberately. the pharma giants that produce them are too rich to care about the cutting costs on something as cheap to produce as amphetamine. but having said that, since it is a drug that is probably gonna be abused anyway, they might not want to make it too 'nice'. People will still buy a racemic mixture so its not like separation of the isomers is totally necessary. It would still be a bitch to do but its not like this is prohibitively true. Drugs like paxil are single enantiomers.

 

[MolokoVelocet]

haha its 5am and i go to edit my coment and when i reload there are 2 new posts. Shouldnt surprise me considering its an amphetamine topic

Adderall contains d-amhpetamine and l-amphetamine in the ratio of 3 and 1 so it's not a matter of difficult isomers separating (why would ephedrine and pseudoephedrine be sold as different medications?). They add it at fixed dose on purpose. Chemists that produce drugs for the black market don't care about separating isomers as far as racemic mixture doesn't completely lose its abuse potential

interesting... thnx Adder for the info (appropriately named )
So they isolate the D first then add the 1/3rd isolated L? So Adderrall (dl-amp, 3/1) costs more to make than isolated d-amph(Dexedrine)!

Aye, the idea that it costs pharmaceutical/drug manifacturers a significant amount of money to isolate the d entiomer(Dexedrine) is rediculous. The idea that it would cost patients significantly more for doctors (im assuming you meant pharm companies/chem manifacturers... as doctors dont tend to synthesize drugs for patients) isolate the D out of DL is rediculous, especially considering Adderall (DL 3/1) is actually isolated d-amph PLUS 1/3rd l-amph (an otherwise waisted byproduct of d-amph isolation, great $ making tactic for the soulless fucking pharmies)

 

[paradoxcycle]

Now that I've got my point across, you should all re-read what I said (reference pdx's post for help if needed, as its purpose was quite apparent.

Again, I must be missing something because I still don't see the point of your original post.

 

[BigBenn]

This thread is great, the discussion is out of control!

Kisps: I want to apologize if i seemed condescending in my post I assumed you had less knowledge of stereochemistry than you did.

You can use optical activity to find percent R and percent S configuration, not exactly purity but verymuch of interest to you.

On a different note let me make sure I have this right...
Adderall is a mixture of stereoisomers and dexidrine is only the dextro?
Is dexidrine more expensive than adderal (on mg for mg basis)?

Whatever you may lack in chemistry knowledge I lack in pharmacology knowledge (particularly with amphetamines). Thankyou for your insight as well as everyone elses. We all walk away from this thread with more knowledge.

 

[BilZ0r]

kisps, you might want to read something outside your textbook... seriously... I was meaning, cite some experimental data.

Adderall contains d-amhpetamine and l-amphetamine in the ratio of 3 and 1 so it's not a matter of difficult isomers separating (why would ephedrine and pseudoephedrine be sold as different medications?). They add it at fixed dose on purpose. C

Best arguement yet...

Still, that leaves one with the question, why?

 

[fastandbulbous]

So they isolate the D first then add the 1/3rd isolated L? So Adderrall (dl-amp, 3/1) costs more to make than isolated d-amph(Dexedrine)!

No. They mix equal doses of d-amphetamine and racaemic dl-amphetamine as the racaemic compound contains a d:l ratio of 1:1. On that basis, if you add 10mg of dexamphetamine to 10mg of racaemic amphetamine the final mixture will contain 15mg of dexamphetamine to 5mg of levo-amphetamine (and for anyone who hasn't noticed yet, 15:5 = 3:1). At no point do they specifically go to the bother of isolating any of the l-isomer. You see, it's very easy to think,"why would they be doing it this way if it costs more" when you just look at one particular way of solving a problem - that's what seems to be happening w.r.t. references to the cost of manufacture of dl vs d-amphetamine. When you're producing tens of millions of doses, all those tiny costs add up and can eventually take a big chunk out of any budget agreed by a pharmaceutical firm to produce a drug

Ill end it with reiterating that it costs pharmaceutical companies/chemical manifactuerers virtually nothing to bulk manifacture and isolate d-amphetamine. So the cost thing you guys keep reiterating has no bearing on a topic regarding pharmaceutical amphetamine manifacure or pharmaceutical amphetamine manifacture PERIOD

.

It doesn't matter how little it costs to manufacture, the isolation of the d-isomer still involves a couple of extra steps, so it's inevitable that d-amphetamine will cost more to manufacture. It's not the cost of the precursors that are important here, but things like the cost of employing staff to carry out the separation of the optical isomers, the extra cost involved in having to operate another quality control program etc.

As to the price having no bearing - when you're manufacturing very large amounts of any drug (no matter how cheap it is to manufacture) the cost becomes an extremely important factor. No firm is going to spend more money then they have to, even firms the size of SmithKline Glaxo etc. So the reason people keep reiterating the cost of the proceedure is because it's the primary motivational factor in any decision that a business takes

 

[yaesutom]

lol - this is one of the most ridiculous threads in a way, but, its got information i didnt know like that l-amphetamine does have those CNS effects (i knew it did something but mostly thought it was crap/waste).

Anyway, starting with the OP,

I've never been a big fan of Adderall due to the cracked out effect it produces. It is often asked why l-amphetamine is still being added to pharms like Adderall, after all it is notorious for producing a lot of negative physical and psychological side effects even at low doses. L-amphetamine, unlike d-amphetamine, does not selectively target dopamine transporters; instead, it targets both the norepinephrine and dopamine transporters. This means that l-amphetamine triggers norepinephrine release as well as dopamine release. If norepinephrine and dopamine have different cognitive effects from person to person, then the cognitive effects of d- and l-amphetamine must also differ from person to person.

That being said, I question any doctor who selectively prescribes Adderall over Dexedrine unless they can adequately explain the psychopharmacology of both enantiomers of amphetamine, and why they prefer one to the other. There is the argument that d-amphetamine has a higher abuse potential than d-, l-amphetamine mixtures, but I think that abuse is inevitable whether the patient is given either medication, they both produce euphoria that is similar enough influence abuse.

First off, at least in the U.S., *most* doctors prescribing Adderall DON'T KNOW SHIT ABOUT HOW IT WORKS. Yeah maybe they passed the necessary tests in school, maybe a doctor is reading this saying in his head "NO..", but in reality .. they might know its "an amphetamine" (lol) but they'll start to get pissy if you start trying to discuss chemistry or why or how this or that drug works etc. (of course, i'm making a generalization here) depends on the doctor (if they have a big EGO or not).

The reason ADDerall is prescribed like candy nowadays I believe is because the drug company representitives have come in all dressed up, with their donuts and free stuff and all that enough times, told by them how good ADDerall works, a bunch of marketing bullshit (by bullshit i'm not saying it doesn't work, just saying how the whole system is bullshit), and WELL nowadays ADDerall is just "standard" and most doctors don't put too much thought into it when writing a new script. I think it seems to be, first some form of Ritalin first, if they come back and bitch, give them Adderall and that usually stops the bitching. Actually now, I think a lot more Adderall is being prescribed right off the bat, probably because "all the other doctors are doing it" and well most people given a choice would choose Adderall over methylphenidate/ritalin (i would!).

I take Dexedrine myself, that 25% l-isomer only does bad things to me if taken more than a couple days. But oh man, it was *difficult* to get my doctor to switch me to Dexedrine, and when he finally did, I had to tell him what to write on the script paper! He told me, "there's no such thing as 10mg dexedrine tablets", told him to "type in dextrostat" on his computer and it came up. Dumbass.. Oh also anytime I get it filled, most pharmacies don't carry it, the tablets or ER capsules, its gotta be pre-ordered, because ... its so rare anyone gets dexedrine anymore.

Another thing - PATENTS. Funny how amphetamine has been around for a long time, dexedrine has, used to be racemic amphetamine available etc. Well, why is there 75% d isomer and 25% l isomer? Gee, lets throw together this,

* 1/4 Dextroamphetamine Saccharate
* 1/4 Dextroamphetamine Sulfate (Dexedrine®)
* 1/4 Amphetamine Aspartate
* 1/4 Amphetamine Sulfate

boss, and we got a new drug! Lets PATENT THIS IDEA! So the drug company gets their patent and markets the hell out of it, charging crazy prices, until their patent runs out... uh oh.. the generic companies start making it for cheaper... so now what? ADDERALL XR!

Adderall XR utilizes the Microtrol® delivery system to achieve the extended-release mechanism. This delivery system incorporates two beads: the first type of bead dissolves immediately and the second type releases four hours later.

So now most doctors are prescribing Adderall XR, which is the same damn thing, except half is released right away, the other half 4 hours later. New patient...lots of crazy marketing and free donuts to doctors - and well thats why most people get prescribed Adderall XR nowadays. If you don't have insurance, and don't know about the generic, i bet most doctors wouldn't even mention it to the patient (if the doc. knows he/she has no insurance).

Really I believe that is mostly the entire reason, to answer your question.

-------------------------

Ok... I may not be right here, but, i'm going to assume that manufacturing Adderall, there is no "separation of isomers" going on.. why would there be? I would think that racemic amphetamine is being made with appropriate precursors, and d-amphetamine is being made separately starting with different precursors so they end up with just the d isomer. No? Then they take each component and mix them together however they do and you then have Adderall. Seems like thats how it would be done, but I may be wrong, just my guess.

 

[Jamshyd]

lol - this is one of the most ridiculous threads in a way, but, its got information i didnt know like that l-amphetamine does have those CNS effects (i knew it did something but mostly thought it was crap/waste).

Yes, I agree. There is a LOT of VERY useful info here (thanks everyone!), though it doesn't seem to pertain to the original post if I understood it correctly, lol.

 

[uacvax]

so dexedrine is less harmful than adderall, while producing the same effects? In essence, adderall is a cheaper to produce version of dexedrine that has more side effects?

 

[cynosure]

The component parts of a salt are ionically, not covalently, bound. This means that, in solution, "conjugated" (ionically bound) amphetamine sulfate ionizes into an amphetamine ion and a sulfate (SO4) ion. This must happen for the drug to work; the amphetamine sulfate won't have any effect ... only amphetamine itself fits in the right place. Different salts ionize at different rates, to different extents, at different pH, and so on. Finding the optimal salt to use is one part of "pharmaceutical formulation chemistry."


So Adderall is "a mixture of salts and isomers." But what is a mixture of half dl-amphetamine and half d-amphetamine? It is just 75% d-amphetamine and 25% l-amphetamine. So Adderall, to put aside the salt issue for a minute, is
really 3/4 dextroamphetamine (d-amphetamine) and 1/4 garbage.


The United States Pharmacopeia (USP) specifies the sulfate salts of amphetamine and d-amphetamine (when not qualified, "amphetamine" means "d,l-amphetamine"), but Adderall adds two additional salts ... the aspartate of amphetamine, and the saccharate of d-amphetamine. So there is a sense in which it contains four different "things," but really, in terms of the alkaloidial bases, it's just 3/4 d-amphetamine and 1/4 l-amphetamine. Adderall is unusual in that most drug products are either USP or NF (national formulary, the United States' other official list of drugs), while Adderall is neither.




The saccharate and aspartate salts in Adderall ionize more slowly than the sulfates. For this reason, Adderall seems to have a "smoother, longer-lasting" effect than, for example, Dexedrine or DextroStat (which are the same thing, but DextroStat comes in 10 mg tablets, while Dexedrine only comes in 5 mg).


Now, in view of that, you might ask, "Then why did they make Adderall-XR, if the formula is already slowly acting just in its nature?" To that, the only answer is ... drug company greed. There is absolutely no need for a sustained-release preparation of Adderall, since the ordinary tablets last plenty long enough to chemically straightjacket disruptive kids in school.

Hope that was helpful.[/QUOTE]

SWIM just had some adderall for the first time last night. The pills I got were 15 mg, and the gel caps were only half full of spansules. Is this normal? Seemed strange to me, but I was told (by SWIM's source) that this was normal. Tell me the truth someone.
Tried to defeat the time release mechanism by crushing the pills. Now I undertand why that didn't really work. The rates that the salts ionize....Now certainly there is a way to circumvent this right? Mixing your crushed adderall in a solution with the correct pH. Or just heating and stirring in water? This should allow the salts to ionize fully before ingestion should it now?
I was wondering why it was such a non euphoric, smooth ride...actually, I think that the l-isomer must have hit me first, because I couldn't focus and just felt all racy. Felt like I had ADHD, then after 2+ hours things were groovy...for a long long time.
So can anybody answer these 2 questions?

 

[Morninggloryseed]

Different things work differently for different people. I can not tolerate dexedrine. Racemic amphetamine, or the adderall preperation, is the only one comfortable to me. Guess the 'garbage' does something.

Benzedrine (l-amphetamine) was quite popular for a time.

Not eveyone response to medication the same.

 

[BilZ0r]

^ Yeah, the idea the l-amphetamine is without effect is a crazy one.

 

[kisps]

Different things work differently for different people. I can not tolerate dexedrine. Racemic amphetamine, or the adderall preperation, is the only one comfortable to me. Guess the 'garbage' does something.

Benzedrine (l-amphetamine) was quite popular for a time.

Not eveyone response to medication the same.

Thank you, this illustrated my original point. In morninggloryseed's case, the 25% of l-amphetamine in Adderall proved to be more beneficial to him than a 100% d-amphetamine pharm. I don't think its intelligent to refer to l-amphetamine as 'crap', its all subjective.

If norepinephrine and dopamine have different cognitive effects from person to person, then the cognitive effects of d- and l-amphetamine must also differ from person to person.

From a recreational use perspective, Adderall may not have as great of a reputation as Dexedrine or any other d-amphetamine pharm, but this does not make it 'crap'. Whenever I consume it recreationally, I feel like i'm cheating my health in the pursuit of a high from a medication that obviously was not be taken in excess. High doses of Adderall are obviously going to provoke negative side effects, 25% of it was intended to be of possible benefit over d-amphetamine alone. Rationally speaking, if you're taking a drug that is 75% euphoria-inducing, and 25% is supposed to be of possible benefit if taken as prescribed, than one should expect no more than 75% of a positive effect if taken in excess.

 

[DadeMurphy]

Benzedrine was racemic amphetamine:
http://en.wikipedia.org/wiki/Benzedrine

 

[BilZ0r]

^ It seems that way...

 

[Jamshyd]

Benzedrine (l-amphetamine) was quite popular for a time.

I am not one to split hairs.. just want to get my info right.. but wasn't Benzedrine an Amphetamine Racemate?

 

[cynosure]

Hey about defeating the time release mechanism of the salt isomer mixture? How do you get them to ionize effectively. I read a post about lemon juice overnight. I would think, just gentle heating in water would work. The salts will ionize if there is enough solvent, and heating will speed that up. So you should be able to get all of the amphetamine heating at the same time this way. what do you guys think?

 

[BilZ0r]

^ Yes, you're right Jamshyd, it is.

 

[fastandbulbous]

How do you get them to ionize effectively. I read a post about lemon juice overnight. I would think, just gentle heating in water would work. The salts will ionize if there is enough solvent, and heating will speed that up.

No because the ion that is formed from the H+ transfer to the amine function is bound to a copolymer (usually -COOH or -SO3H) so isn't going anywhere. It's dependant upon the amphetamine being transfered from the polymer bound acid function to an ion in solution, like Cl- in the stomach (the difference in pH will effect the speed at which the amphetamine is turned into a soluble salt

 

[Morninggloryseed]

In that case, wikipedia has incorrect information. A look at an old PDR show benzedrine was l-amphetamine.