|Systematic (IUPAC) name|
|Mol. mass||415.528 g/mol|
SoRI-20041 is an "antagonist-like" allosteric modulator of amphetamine-induced dopamine release (in contrast to the related research chemicals SoRI-9804 and SoRI-20040, which are "agonist-like"). SoRI-20041 is believed to be the first example of a drug that separately modulates uptake versus release in the dopamine transporter (possibly showing how inward and outward transport represent distinct operational modes of DAT); it produced the same effects as SoRI-20040 and SoRI-9804 in uptake assays and binding assays, inhibiting the re-uptake of dopamine, but did not modulate d-amphetamine-induced DA release by inhibiting that as well, like 'agonists' of the series do.
This suggests the possibility of simultaneous action & increase of indirect-agonism through the dual-action of DRA & DRI efficacy existing together. Greatening of the inhibition of re-uptake at synaptic dopamine concentrations without interference to the flow of release of dopamine from amphetaminergic phosphorylation at the transporter so effected. This overcomes the obstacle of a compromised binding site which would be rendered unusable through the action of amphetamine. A site which conventional dopamine re-uptake inhibitors (such as cocaine or methylphenidate) would otherwise ineffectively target on each specific transporter so effected by amphetamine. Making this an example of a DRI that does not have a mutually exclusive functionality against DRA action at individual instances of DAT.
- Rothman, R. B.; Dersch, C. M.; Ananthan, S.; Partilla, J. S. (2009). "Studies of the Biogenic Amine Transporters. 13. Identification of “Agonist” and “Antagonist” Allosteric Modulators of Amphetamine-Induced Dopamine Release" (pdf). The Journal of Pharmacology and Experimental Therapeutics 329 (2): 718–728.