kisps said:
I wasn't asking a question, I was just explaining why l-amphetamine is used in conjunction with d-amphetamine. I highly doubt that the process of separating the isomers is difficult enough to influence doctors to just prescribe Adderall.
So what was the purpose of your post? Do you have a question? Like everyone above me mentioned, separating optical isomers is pretty difficult and costly.
Do you understand what an "isomer" is? I'm assuming you don't so I'll explain briefly..
Organic molecules are mostly made of carbon atoms, arranged in different ways. A carbon atom must have four bonds to it. A double bond, then, counts as two, and a triple bond counts as three. But most bonds are single bonds.
When a carbon atom in a molecule has four completely different things attached to it, that atom is called a "chiral center" ... "chirality" is the property of "handedness," so your left and right gloves are chiral copies of one another: you cannot superimopose them without flipping one over (rotating it through the third dimension), and even then you're not really superimposing them. They're just different. Chiral centers give rise to isomers because the order of the four things attached to them gives rise to molecules that are different in three-dimensional space (even though they look the same when the structure is drawn on paper).
Now, the idea of "d" and "l" isomers only applies to simple molecules with only one chiral center. If a molecule has two, or three, or more, chiral centers, it is
meaningless to talk about "d" or "l" isomers of it ... it doesn't just have two
isomers, it has 2^n isomers, where n is the number of chiral centers. In this case, chemists specify the "absolute configuration," by using either + and -, or "R" and "S," to specify the configuation around each chiral carbon atom.
But if there is only one chiral center, as is the case with amphetamine, which is a very simple molecule (the alpha-carbon is chiral), then there will only be two isomers. If we make a solution of each of the purified isomers, we'll find that the solution of one of them will rotate a beam of polarized light to the right. The isomer that does this is called the "dextrorotatory" one, from the Latin for "right-rotating," and abbreviated with the word "dextro" or a lower-case "d" as a prefix. The other isomer will rotate a beam of polarized light to the left. This isomer is called "levorotatory," from the Latin for "left-rotating," and abbreviated with the word "levo" or a lower-case "l" as a prefix. Because the isomers are differentiated from one another by their effect on light, they are called "optical isomers."
Optical isomerism has nothing to do with absolute configuration. In other words, you can't deduce the shape of the molecule in space from which way it rotates polarized light. It's a convenient kind of designation that is left over from the days when isomerism and chemical structure were just beginning to be understood.
When a drug, such as amphetamine is synthesized, as a general rule, the product will be a 50:50 mixture of the dextro and levo isomers (called a "racemic mixture"). The designation "d,l-amphetamine" is shorthand for "racemic amphetamine," that is, a half-and-half mixture of d-amphetamine and l-amphetamine. It is possible to synthesize the pure isomers directly, or the racemate can be resolved into them.
In pharmacology, different isomers often have different effects in the body. In the case of amphetamine, d-amphetamine is at least five times as potent as l-amphetamine in eliciting the release of dopamine, while l-amphetamine tends to release more norepinepherine and thus causes far less central stimulation and euphoria, and more unpleasant side effects like high blood pressure and sweating.
Now, regarding salts. Salts have nothing to do with isomers. Drugs are generally alkaloids, and, to make them soluble in water and easily absorbable, they are often prepared as salts. An alkaloid, by definition, used to be any naturally occuring compound with a nitrogen atom in it (now, the "naturally occuring" part of the definition has been dropped). The nitrogen confers a positive charge on the molecule, so it becomes possible to precipitate it from solution by adding a strong acid to form a salt of the drug (a salt is the product of the reaction of an acid and a base, to simplfy somewhat). With amphetamine, the acid used in pharmaceutical manufacturing is usually sulfuric acid (H2SO4), and this results in amphetamine sulfate being produced.
The phosphate, prepared by using phosphoric acid, is much better suited for injection, but injectable amphetamines are illegal in the US.
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.
Why were the other two, non-USP, salts added? Adderall was not always called "Adderall." The formula was originally named "Obetrol," back when amphetamines were handed out like candy as "diet pills." Amphetamine went on the market in the 1930's, and d-amphetamine in the 1940's, so they've both been off-patent for decades. The original manufacturer wanted something to distinguish Obetrol from the dozens of other amphetamine preparations on the market at the time, and they hit on this multiple salt idea. Still, although it was widely used, Obetrol was never as popular as Dexedrine or Biphetamine (black beauties).
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.
) reply, I gave into my defensive side and am now writing this, an explanation of my original post. I posted this to provide a basis for future understanding of a much more intricate, involved subject.
), as its purpose was quite apparent.
![:\](https://bluelight.org/xf/BL_Images/Orig_Emoji/wrygrin.gif "wry grin :\")
