nuke
Bluelighter
- Joined
- Nov 7, 2004
- Messages
- 4,191
It's pretty clear from several different studies that MDMA and MDA have pretty much no affinity for human SERT.
Cloned human SERT
MDA: 107,000.000000nM, hot ligand 3H-5HT (Jones DC, et. al., 2004)
MDMA: 102,000.000000nM, hot ligand 3H-5HT (Jones DC, et. al., 2004)
> 10,000.000000nM, hot ligand 3H-CITALOPRAM (PDSP certified data)
The story is similar for NET and DAT.
In fact, amphetamine has much higher affinity for human SERT:
Cloned human SERT
d-AMP: 1,765.000000, Functional assay (Rothman RB, et al., 2003a)
So, what's the story? Does MDMA simply not displace 5HT, DA or NE somehow? Are functional assay the only clear way to get reasonable affinity values for amphetamine-type monoamine releasers? This latter question is curious too, since d-AMP displaces very well other substrates at the dopamine receptor. Something strange appears to be happening that's not in line with the theories produced so far as to pharmacological mechanism of action, which were all mostly based on data from lower order mammals.
Cloned human SERT
MDA: 107,000.000000nM, hot ligand 3H-5HT (Jones DC, et. al., 2004)
MDMA: 102,000.000000nM, hot ligand 3H-5HT (Jones DC, et. al., 2004)
> 10,000.000000nM, hot ligand 3H-CITALOPRAM (PDSP certified data)
The story is similar for NET and DAT.
In fact, amphetamine has much higher affinity for human SERT:
Cloned human SERT
d-AMP: 1,765.000000, Functional assay (Rothman RB, et al., 2003a)
So, what's the story? Does MDMA simply not displace 5HT, DA or NE somehow? Are functional assay the only clear way to get reasonable affinity values for amphetamine-type monoamine releasers? This latter question is curious too, since d-AMP displaces very well other substrates at the dopamine receptor. Something strange appears to be happening that's not in line with the theories produced so far as to pharmacological mechanism of action, which were all mostly based on data from lower order mammals.