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  • AADD Moderators: swilow | Vagabond696

How much Noradrenaline does MDMA release ?

D

Dr. Beat

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Apr 1, 2002
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On rhodium the have a great pharmacology document, and in it they say that MDMA releases 10 times more seratonin than dopamine or noradrenaline, yet recently on here, some guy put up a table with the releasing ability of amphetamine, Meth, and MDMA, and it was saying that MDMA directly releases seratoin and noradrenaline in fairly similar amounts, and is a weak direct dopamine releaser. (dopamine is released indirectly - eg. 2A receptor, 1B, and so on)

Which one is true ?

And in the rhodium document, it says that MDMA S(+) releases alot more seratonin than R(-), but that S and R relrease the same amount of noradrenaline, yet else where I have read that only the S(+) releases lots of noradrenaline, and the R(-) dose not, and it was saying that the S(+) gives the wide eyes and jaw grinding, but that R does not at all, indicating little or no noradrenaline release.

Which one is true?

And recently some guy on here said that the racemate of methamphetamine releases 10 times more noradrenaine than dopamine.

does l-methamphetamnie release lots of noradrenaline ?

thanks.
 
All the common amphetamines release more noradrenaline than dopamine. Though people comment on the dopamine releasing abilities of methamphetamine, it releases more noradrenaline.

What you're referring to is the binding efficacies of each (or what was referred to, rather)

--
Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS. "Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin." Synapse. 2001 Jan;39(1):32-41.

A large body of evidence supports the hypothesis that mesolimbic dopamine (DA) mediates, in animal models, the reinforcing effects of central nervous system stimulants such as cocaine and amphetamine. The role DA plays in mediating amphetamine-type subjective effects of stimulants in humans remains to be established. Both amphetamine and cocaine increase norepinephrine (NE) via stimulation of release and inhibition of reuptake, respectively. If increases in NE mediate amphetamine-type subjective effects of stimulants in humans, then one would predict that stimulant medications that produce amphetamine-type subjective effects in humans should share the ability to increase NE. To test this hypothesis, we determined, using in vitro methods, the neurochemical mechanism of action of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), (+)-methamphetamine, ephedrine, phentermine, and aminorex. As expected, their rank order of potency for DA release was similar to their rank order of potency in published self-administration studies. Interestingly, the results demonstrated that the most potent effect of these stimulants is to release NE. Importantly, the oral dose of these stimulants, which produce amphetamine-type subjective effects in humans, correlated with the their potency in releasing NE, not DA, and did not decrease plasma prolactin, an effect mediated by DA release. These results suggest that NE may contribute to the amphetamine-type subjective effects of stimulants in humans.
Click to expand...
 
The amount of (+/-)-MDMA which will release half of the maximal amount of monoamines goes 77.4nM for noradrenaline, 56.6nM for serotonin and 376nM for dopamine.

These values are from isolated synaptosomes, just the ends of neurons, which can't fire action potentials.

As you say, there is some evidence that MDMA-induced dopamine release is in part mediated by action-potential dependent mechanisms... probably through the 5-HT2A receptor. So, in a whole animal, MDMA mediated dopamine release is probably a bit higher than those numbers above would indicate, but then it gets very hard to actaully QUANTIFY release.

As the paper cited by velocideX states, MDMA and (meth)amphetamine release a lot of noradrenaline.
 
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