Ritalin VS Adderall

Bottom Line:

Ultimately Ritalin and Adderall belong to the same class of compounds, the phenethylamines. Ritalin is one of the trade names of the compound methylphenidate. It is also sold as Concerta and Biphentin which differ in dose and have small modifications to control release of the active compound. Adderall is a mixture of right and left handed enantiomers of amphetamine. Dexedrine is purely the right handed enantiomer of amphetamine, while Vyvanse is the right handed enantiomer with lysine attached, thus making it an inactive prodrug. All of these are stimulants and act on the release and reuptake of dopamine and norepinephrine. They are used primarily in the treatment of ADHD and narcolepsy.

Memory Aids:

Adderall is Amphetamine

Details:

I have to be honest right off the bat and say that this post is cobbled together mainly from multiple articles on Wikipedia.

Now before we start, we need to do a bit of chemistry …

Phenethylamine is the parent compound of the drugs we are talking about today. Phenethylamine contains a phenyl ring (it looks like benzene if you remember organic chemistry) with an ethyl group coming off which is attached to an NH2. To build child molecules from this parent you can stick various parts onto the structure which yields a class of compounds called the “substituted phenethylamines”.

One of the substituted phenethylamines is amphetamine. It turns out that “amphetamine” is short for alpha‑methylphenethylamine, which you can see from the name, is one of the simplest substituted phenethylamines. It exists as left handed or right handed enantiomers (levorotary or dextrorotary AKA levoamphetamine or dextroamphetamine). It also turns out that amphetamine is the parent compound for its own class of drugs, the substituted amphetamines (which you can make by sticking various things onto the amphetamine molecule).

So as far as family trees go, phenethylamine is the granddaddy who had a whole pile of children. One of those is amphetamine who went off and had a whole pile of children of his own.

Methylphenidate is a substituted phenethylamine, but not a part of the amphetamine family. It is synthesized from piperidine (which is found in black pepper and used in the synthesis of a whole whackload of other drugs).

Adderall is the trade name for the combination of 75% dextroamphetamine and 25% levoamphetamine. Since the components of Adderall are just pure amphetamine I suppose the generic name for Adderall is just “amphetamine”. The drug Dexedrine is pure dextroamphetamine, while Vyvanse (lisdexamfetamine) is dextroamphetamine with the amino acid lysine stuck to it. This makes Vyvanse a substituted amphetamine.

Now that all that pesky chemistry is out of the way, we can see why Ritalin (methylphenidate) and Adderall (amphetamine) have similar effects, they are both phenethylamines.

Methylphenidate

Methylphenidate has been used since the 1950s in the US and (as I’m sure you know) use has skyrocketed in recent decades. It is a stimulant and inhibits the reuptake of dopamine and norepinephrine (dopamine more-so) by blocking the reuptake transporters. Like amphetamine, methylphenidate has left handed and right handed enantiomers as well. The right handed, or dextrorotary enantiomer is more effective which has led to the production of pure dextrorotary methylphenidate or “dexmethylphenidate”. This is marketed as Focalin or Attenade.

It is used in the treatment of ADHD (attention deficit hyperactivity disorder) and narcolepsy. It has also been used in cases of refractory depression and as a performance enhancer (both athletic and cognitive).

Amphetamine

Amphetamine was first synthesized in the late 1800s and began being used medically in the 1930s. It is a stimulant and, like methylphenidate, it increases the amount of dopamine and norepinephrine in the synaptic cleft. It has several different mechanisms though. Wikipedia has an excellent graphic on the amphetamine and the Adderall page that explains some of the proposed mechanisms of amphetamine on dopamine, but I can summarize. Amphetamine stimulates the TAAR (trace amine associated receptor) molecule which then affects the dopamine transporter in a few possible ways. It could make the transporter work in reverse mode and push dopamine back into the synaptic cleft rather than reuptake it. It could also cause internalization of the dopamine transporter leaving fewer transporters along the membrane to reuptake dopamine. Amphetamine is also a competitive antagonist for dopamine at the dopamine receptor, so even if the receptor is functioning in reuptake mode, it may be too clogged with amphetamine to remove dopamine from the cleft. It also displaces dopamine from pre-synaptic vesicles, pushing that dopamine into the cytosol and making it more likely get extruded into the cleft by a dopamine transporter working in reverse mode. Similar mechanisms have been proposed for the effect of amphetamine on norepinephrine. Dextroamphetamine has more potent central effects, but levoamphetamine has more potent cardiovascular and other peripheral effects. It also has a slightly longer half-life.

As with methylphenidate, it is used in the treatment of ADHD, and narcolepsy. It has off-label use in depression and as a performance enhancer (both athletic and cognitive). It also has some use in obesity. Amphetamines are the infamous “go pills” used by the US military to keep pilots awake on long missions (you can read about that here).

The CADDRA guidelines contain the Canadian recommendations for ADHD treatment. You can click here to see their excellent graphic on ADHD medications which list all the drugs I’ve talked about. They publish a large guideline document, but Chapter 7 is of particular relevance to today’s topic.

Most sources don’t give strong evidence that one drug is “better” than another, but rather the medications are just “different”. Choice of drug may just come down to patient characteristics (age, history, symptoms), patient preference, physician preference, side-effect tolerance, and so forth.

References:

Wikipedia’s Ritalin (methylphenidate) page

Wikipedia’s Adderall page

CADDRA ADHD medication graphic

CADDRA ADHD Guidelines 2011 -Chapter 7 – Pharmacological Treatment of ADHD

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