EC50 values racemic amphetamine

[Nephtys]

Hey,

I'm currently studying/trying to understand amphetamine's neurotoxicity.
Dextro-amphetamine and racemic amphetamine are the common forms around here.
Serotonin release is a very important part I'm trying to understand.
Dex has very little release, while racemic amphetamine has more to do with serotonin.
I was searching for the EC₅₀ values for SERT release:

(+)-Amphetamine
Release SERT
EC50 (nM ± SD)
1,765 ± 94

Source: Rothman RB, Baumann MH. (2006) Therapeutic Potential of Monoamine Transporter Substrates. Current Topics in Medicinal Chemistry. 6(17), 1845-1859

Dex doesn't release much serotonin...
I'm stuck at racemic amphetamine.

Has anyone an idea where I could find the EC50 values for (±)-amphetamine?

 

[sekio]

If you find the EC50 for (-) amphetamine, simply average the 2 numbers.

Even this page only has (+)- amp. perhaps you need to dig around in the journals.

 

[Nephtys]

I'll try digging till the end of the internet. This issue has followed me way too long...

 

[endotropic]

Does this help?

http://pdsp.med.unc.edu/pdsp.php?kn...=&KiLess=&kiAllRadio=all&doQuery=Submit+Query

 

[pr0d1gy]

Bindingdb has the affinity for slc6a4 in rats listed. There seems to be less info available for (-)-amphetamine as opposed to its enantiomer.

I'm not really that clear in regards to what you are trying to look into here and what it has to do with amphetamine neurotoxicity as a whole. If you were to expand on that; it might be possible for us to supply you with relevant information beyond the scope of what you asked for initially

 

[Epsilon Alpha]

Very good question, I've personally been looking at it's metabolites' affinity for DA neuronal markers.

 

[ebola?]

I think it could have something to do with the combination of + and - amp that potentiate each other.

How could the activity of (-)-amphetamine change the activity of (+)-amphetamine at SERT?

This has been shown to happen by Shulgin with MDMA

This is a synergy of qualitative subjective effects stemming from the differing activities of the two stereoisomers of MDMA. (-)-MDMA has far more dramatic psychoactivity than (-)-amphetamine.

Subjectively, with amphetamine and its N-methylated derivative the dextroratory isomer is preferred in terms of effects profile although the racemic form has resulted in more potent and long lasting effects.

On a per-milligram basis, the +isomers of either are far more potent. As for increased duration, it could be that the (-)-isomers tie up relevant metabolic enzymes.

ebola

 

[Nephtys]

Thanks, for the info
The ec50 values are just a minor detail that got my attention.

The distinction in isomers on the other hand is something I'll have to thorougly research.