Just curious. I know that every person reacts differently to them, but since they're different drugs I assume they have a different mechanism of working somehow?

I have no idea :-) I am sure someone will know though..

Methylphenidate blocks re-uptake of dopamine and norepinephrine (noradrenaline to non-americans) in certain areas of the brain.

Amphetamines are agonists of these two chemicals, cause release of these things. And/or actually bind to the receptors as if these chemicals were DA and NE.

At least that's my understanding.

I dont' think it is just the chemical.

For example, users say that Ritalin is very different than Concerta (yet both are 'Methylphenidate').

And users say (myself included, that) Dexedrine is very different than Adderall (yet both are 'dextroamphetamine').

Yes, but their mode of action remains the same even if the effects are different because of dosage method.

And personally, I'm starting to wonder which is more harmful.

Methylphenidate traps your dopamine, this is unnatural, but amphetamines release your dopamine. Both of these have profound physiological effects on the brain that I am sure present for years afterwards. I'm starting to assume that the depression I got for 10 freakin years after going off of Ritalin was because it fried my brain's reward pathways I couldn't experience joy anymore without chemical assistance! ARG!

Methylphenidate blocks re-uptake of dopamine and norepinephrine (noradrenaline to non-americans) in certain areas of the brain.


Also it does not inhibit the release of dopamine. Wellbutrin
has a similar action of methylphenidate but it inhibits the release of of
dopamine. Which maybe why its generally less effective ADHD drug.



Amphetamines are agonists of these two chemicals, cause release of these things. And/or actually bind to the receptors as if these chemicals were DA and NE.

At least that's my understanding.

I'm not sure if agonist action is correct. I think amphetamines do stimulate the
release of DA and NE.

Oh sorry, did I use the wrong word, see I did say "cause a release" is that antagonistic action rather than agonist?

Oh sorry, did I use the wrong word, see I did say "cause a release" is that antagonistic action rather than agonist?

I think agonist means that it would effectively act like dopamine or noradrenaline itself. I guess an antagonist would compete with dopamine and
noradrenaline but would not have the same effects. Which means neither terms apply. Oh I assume there could be multiple actions from amphetamines but the primary I think it just stimulates release. Not sure if there is a fancy word that
means "stimulates release".

Okay, then I'm pretty sure amphetamines are agonists then, they do act like dopamine on the brain. In addition to releasing. Or correct me if I'm wrong.

I don't think anyone has ever found a definitive answer to this question. It's a good question though. Both pretty much do the same thing in the brain but go about the process a little differently. Hence why some people respond differently to one class of meds vs the other.

J

I am often a grammar nazi and correct friends anytime they are wrong, but I don't quite feel like getting into the argument over differences in diction. I can though validate that amphetamines stimulate the release of dopamine, and to a lesser extent norepinephrine, from what I've read. Since amphetamines have a more profound and concentrated effect on the release of dopamine, it is prone to being easily addictive.

Methylphenidate works similarly to amphetamines only in regards to focusing on dopamine, and to a lesser extent norepinephrine, but instead blocks reuptake. This is the mechanism also used by cocaine, which is a stimulant too and similar in structure to methylphenidate. It too can be addictive because it concentrates on domapmine.

Wellbutrin seems to be more balanced in how it works on dopamine and norepinephrine (maybe slightly more for norepinephrine) and I believe it blocks the reuptake of those. This is why it seems to work well as an adderall booster because while adderall forces more dopamine to be excreted, reuptake inhibition like that of Wellbutrin will allow more to be absorbed.

The method of which the dosage is administered to the body makes a lot of difference to what effects might occur and whether it is therapeutic or not. Adderall XR was a lot smoother for me than adderall obviously. My previous doctor also had me try the generic of Ritalin SR which did not seem to give me the desired benefits I was looking for. It did not improve my concentration but kept me alert and awake even if I went to sleep late the night before. I knew then to keep looking on the Adderall/amphetamines side of the treatment spectrum. I sometimes get a tremor in my hands when upping or changing the dosage of adderall, which contains 4 amphetamine isomer varients. From reading on these forums, it seems the racemic isomer of dextroaphetamine can be blamed for the tremor so I would like to switch to dexdrine.

Those are my experiences and just how I see each method of action relating to me and how I responded to each. While it may seem methylphenidate is methylphenidate, there are subtle differences that give a slightly different effect. Although, if you notice some benefit but that it's still not perfect, keep searching on that path like a dog might continue to head in a direction after picking up on a scent. Good luck, and I hope my rambling helps! :)

Oh hot diggity, thank you everyone who has answered thus far.

So adderall is either pretending to be dopamine/neurolongword, or is making them fire off. Ritalin/ect. are stopping the dopamine transmittors from disappearing in the little holes they go into... or something like that. LOL, I saw it in a movie in psychology class about antidepressants that are reuptake blockers. Interesting.

Mincan, you think you actually fried your dopamine receptors? How much ritalin were you on?

Hey michael, when people say that XR is "smoother" what do they mean exactly? I was offered XR by my doctor today but I said no because I like to break them in half. Maybe I should have taken it. Hmm

Mincan, you think you actually fried your dopamine receptors? How much ritalin were you on?

It's not so much how much I was on, but the fact I was on it for 6 years. I believe I was on about 10mg 2x daily as a child, breakfast and lunch, but I don't remember, I was also on Clonadin at supper to sleep (still didn't sleep till very early morning and up at 5:30am every morning for years, wish I was like that now!)

I don't know, all I know it about after I stopped taking it I was depressed even now. It could be because I was sad at first at being unmedicated and it just morphed as I had more ****-ups in my life. I don't know.

Wellbutrin seems to be more balanced in how it works on dopamine and norepinephrine (maybe slightly more for norepinephrine) and I believe it blocks the reuptake of those. This is why it seems to work well as an adderall booster because while adderall forces more dopamine to be excreted, reuptake inhibition like that of Wellbutrin will allow more to be absorbed.

Wellbutrin is also a dopamine antagonist though, it prevents dopamine from being released in the brain, so how could it be a stimulant booster? That's why it works on smoking cessession, it stops the dopamine release in the nucleus accumbens associated with nicotine consumption/addiction.

Wellbutrin is also a dopamine antagonist though, it prevents dopamine from being released in the brain, so how could it be a stimulant booster?

For starters, Wellbutrin could be quite a stimulant booster due its amphetamine like abuse potential.

In fact, Wellbutrin is the only FDA approved antidepressant to ever show an amphetamine like abuse potential after it was observed during preclinical trials that animals would actually substitute bupropion for amphetamine in a drug-discrimination task, and in another study in which it was self-administered by monkeys intravenously.

In hindsight, it's easy to see that this is something that should have been looked at more closely with respect to the human animal, and the fondness that some humans have when it comes to things with addictive qualities. Like described in the link below.

http://www.entrepreneur.com/tradejournals/article/169596584.html

Yes, but other than the elevated levels of dopamine is causes through re-uptake inhibition, no other substances are allowed to release dopamine, this is it's other useful property.

Being a dopamine reuptake inhibitor does not impact the ability of a dopamine agonist from being able to activate dopamine.

For example, I will bring this thread back on topic by showing how this works with methyphenidate and amphetamine. ;)

As you probably know, methylphenidate is considered to be more of a dopamine reuptake inhibitor, while amphetamine is considered to be more of a dopamine agonist.

When my Dr allowed me to experiment with a combination of Ritalin & Dexedrine, and with Focalin & Dexedrine, and with Focalin & Desoxyn, it became clear to me then how underrated the actual synergistic effect of these combinations actually is.

For example, my normal dose of Dexedrine, or Desoxyn would be 20mg. However, I found that by taking 10mg of either of those two amphetamines along with a small dose of Ritalin, or a small dose of Focalin that I was able to achieve the desired effect with an overall lower dose of medication.

The reuptake properties of the methylphenidates allowed the dopamine that had been activated by the amphetamine to saturate my synapse for a longer period of time, thereby allowing me to experience the benefits of a larger dose of amphetamine than I had actually consumed.

You can break your XR in half my doctor told me. You just sprinkle the amount you want on apple sauce or something comprable and swallow without chewing. As far as being smooth -- it means that you don't get "hit" with a sudden rush of the medication and a sudden drop off as the medication wears off. It builds up and drops off more gradually which is a nice difference.
Oh hot diggity, thank you everyone who has answered thus far.

So adderall is either pretending to be dopamine/neurolongword, or is making them fire off. Ritalin/ect. are stopping the dopamine transmittors from disappearing in the little holes they go into... or something like that. LOL, I saw it in a movie in psychology class about antidepressants that are reuptake blockers. Interesting.

Mincan, you think you actually fried your dopamine receptors? How much ritalin were you on?

Hey michael, when people say that XR is "smoother" what do they mean exactly? I was offered XR by my doctor today but I said no because I like to break them in half. Maybe I should have taken it. Hmm

Ok ok ok, now I'm confused. So, conclusion is amphetamines kill neurons and methyphedinate doesn't because they work.......????

Ok ok ok, now I'm confused. So, conclusion is amphetamines kill neurons and methyphedinate doesn't because they work.......????
No.

Amphetamines have only been shown to kill neurons in drug addicts who have taken high doses (400mg and higher) on a regular basis for extended periods of time.

Amphetamines have never been shown to kill neurons in people taking them as prescribed at therapeutic doses, and some of the people who use them like this have been doing it for decades.

Methylphenidate has not been shown to kill neurons because there has never been an epidemic of methylphenidate addiction like there has with amphetamine addiction. As a result, the research in this area has been done with amphetamines.

"Dopamine agonist" typically refers to drugs that stimulate the receptor end of the system, and are typically used in Parkinson's disease and RLS, e.g. pramipexole (Mirapex), bromocriptine, cabergoline, Requip, etc.

I have seen the term applied to amphetamine, but I don't favor it personally, nor IME do most doctors and researchers. I'd just say it "directly releases dopamine and norepinephrine". Amphetamines have a pretty unusual mode of action that's not really duplicated by much else, one of these "elses" being phenethylamine, an endogenous ligand.

Amphetamine = Alpha-methyl-phenethylamine

conclusion is amphetamines kill neuronsEr, no. I end up saying this a lot, but there's no evidence whatsoever of this occurring at therapeutic doses in humans.

Methylphenidate has not been shown to kill neurons because there has never been an epidemic of methylphenidate addiction like there has with amphetamine addiction. As a result, the research in this area has been done with amphetamines.

Funnily enough, there's a good body of research now showing that agents which block the dopamine transporter (like methylphenidate) actually prevent high-dose amphetamine neurotoxicity when added. Theoretically it has something to do with moving the dopamine out of the synaptic cleft ...

I thought an agonist (in this case) was a drug that activated dopamine transporters.

This is where I first read about it. http://exploration.vanderbilt.edu/news/news_galli.htm

Did I missunderstand something? Sorry if I did.

Senator, I served with Jack Kennedy: I knew Jack Kennedy; Jack Kennedy was a friend of mine. Senator, you're no Jack Kennedy.(Lloyd Bentsen's reply to Dan Quayle in a 1988 presidential debate)

I've used a dopamine agonist (bromocriptine) its no amphetamine.

Lloyd Bentsen! LOL! That's hilarious.

Believe it or not, that was the very first election I was old enough to vote in.

Hahahaha. Gotta search that debate on youtube.

This is all very interesting to me. Very, very interesting. I'm very grateful for these replies, but I have very little to say back. Other than that I guess that it's very nice to know that the people frying their dopamine receptors were taking 400 mg a day of the stuff, so I shouldn't worry about that as much, and very handy to know that XR can also be split.

And that's a very usefull cartoon Lars, but it's also kinda scary since it reminds me that I'm actually doing stuff to my brain.

And that's a very usefully cartoon Lars, but it's also kinda scary since it reminds me that I'm actually doing stuff to my brain.
I'm glad you like it.

Don't be scared though.

You're doing stuff to your brain everytime you look, touch, taste, feel, smell, or think due to neural pathways so numerous that it literally boggles the mind. Pardon the pun. :)

Seriously though, I know what you mean about feeling scared about the old noodle, but after being on these things for so long, I feel quite healthy, and I feel like my mind is sharper than at any other time in my life. I've been on the Deans list for the last 4 years. I have a 3.25 GPA, and it would have been higher if I had only stopped drinking sooner, but I digress.

I know that there is no way that I could have ever succeeded academically without the help of my medication, because prior to taking meds I flunked out of high school and got my GED about 20 years ago this very year. I was diagnosed in Febuary of 1992, which was 4 years after my final year in high school.

Wow, I used the word "very" eight times in my last reply! Man.

Thanks, that's true. Everytime my eyes open, I'm doing all kinds of 'seeing' from the back of my head and all. I guess it's scary doing something to my brain that isn't the natural function.

You're in school now then?

I thought an agonist (in this case) was a drug that activated dopamine transporters.

You are correct in this definition (well, receptors instead of transporters). Amphetamine is not a dopamine agonist because amphetamine does not directly bind to and activate dopamine receptors. The dopamine is still doing the dirty work, but the amphetamine gives the dopamine a little push to get out there and do something for a change.

http://en.wikipedia.org/wiki/Dopamine_agonist

You are correct in this definition (well, receptors instead of transporters). Amphetamine is not a dopamine agonist because amphetamine does not directly bind to and activate dopamine receptors. The dopamine is still doing the dirty work, but the amphetamine gives the dopamine a little push to get out there and do something for a change.

http://en.wikipedia.org/wiki/Dopamine_agonist

Thanks man. ;)

I love to learn.

For starters, Wellbutrin could be quite a stimulant booster due its amphetamine like abuse potential.

In fact, Wellbutrin is the only FDA approved antidepressant to ever show an amphetamine like abuse potential after it was observed during preclinical trials that animals would actually substitute bupropion for amphetamine in a drug-discrimination task, and in another study in which it was self-administered by monkeys intravenously.

In hindsight, it's easy to see that this is something that should have been looked at more closely with respect to the human animal, and the fondness that some humans have when it comes to things with addictive qualities. Like described in the link below.

http://www.entrepreneur.com/tradejournals/article/169596584.html

I think the reason why Wellbutrin is not a controlled substance is because of the risk of seizure associated with taking high doses of it. It is likable, but is also dangerous when used recreationally.

I don't mean to take this discussion off topic, but this is something that I've researched a bit on in the past...

I think the reason why Wellbutrin is not a controlled substance

Wellbutrin inhibits the release of dopamine. Cocaine, amphetamines and methylphenidate do not. Its likely not a controlled substance because it has fairly low abuse potential. People who try to abuse it are taking advantage of the fact that it is very poorly orally absorbed(5-20%). And a bottle of such pills intended for oral use would be 5-20 times more potent if used intra-nasally. That makes it economically/logistically possible to use large doses for a person who has no other options but it does not change the fact
its a poor substitute for a stimulant.

Patent on nasal use of wellbutrin.
http://www.patentstorm.us/patents/6150420-description.html

Although there were no seizures reported in this study, bupropion carries a seizure risk of four in 1,000 people at the maximum dose used in this study, which was 400 milligrams per day.

http://www.dukemednews.com/news/article.php?id=3652

That puts the seizure risk is perspective. A drug addict would not be concern
about 0.4% or so risk. The nature of impulsivity and addiction would mean they would tolerate a much greater risk. Surviving multiple seizures is likely
common in the drug abuse world.

This is such very interesting stuff concerning bupropion, but lets try and remember that the OP asked "what do methylphanidates DO differently in the brain than amphetamines?" ;)

That being said, I just want to say that I have enjoyed everyones post in this thread very, very much, but as the moderator of this forum I am required to keep it on topic, even if that means being a buzz kill periodically, so to speak. :o

Seriously, I thank each of you for such informative post. ;)

This is such very interesting stuff concerning bupropion, but lets try and remember that the OP asked "what do methylphenidate DO differently in the brain than amphetamines?" ;)


As stated before bupropion and methylphenidate have ostensibly the same mechanism of action. The difference being bupropion inhibits the release dopamine. To compare two things such as methylphenidate and amphetamines it makes perfect since to compare them to other things as points of reference. Like people have tried (wrongly in my estimation) to compare amphetamines to
dopamine agonist. But it was good that they did mention it.