SoRI-20041

SoRI-20041 is an "antagonist-like" allosteric modulator of amphetamine-induced dopamine release[1] (in contrast to the related research chemicals SoRI-9804 and SoRI-20040, which are "agonist-like").[1] 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 produces the same effects as SoRI-20040 and SoRI-9804 in uptake assays and binding assays, inhibiting the re-uptake of dopamine, but does not modulate d-amphetamine-induced DA release by inhibiting that as well, like 'agonists' of the series do.[1]

SoRI-20041
Identifiers
IUPAC name
  • N-(3,3-diphenylpropyl)-2-phenyl-4-quinazolinamine
PubChem CID
ChemSpider
Chemical and physical data
FormulaC29H25N3
Molar mass415.540 g·mol−1
3D model (JSmol)
SMILES
  • c2ccccc2C(c3ccccc3)CCNc(nc4-c5ccccc5)c1ccccc1n4
InChI
  • InChI=1S/C29H25N3/c1-4-12-22(13-5-1)25(23-14-6-2-7-15-23)20-21-30-29-26-18-10-11-19-27(26)31-28(32-29)24-16-8-3-9-17-24/h1-19,25H,20-21H2,(H,30,31,32)
  • Key:HQPGYRVHOIKOIE-UHFFFAOYSA-N

This suggests the possibility of simultaneous action and increase of indirect-agonism through the dual action of DRA and DRI efficacy existing together. This increases the inhibition of re-uptake at synaptic dopamine concentrations without interfering in the flow of release of dopamine from amphetaminergic phosphorylation at the affected transporter. This overcomes the obstacle of a compromised binding site that would be rendered unusable through the action of amphetamine. Conventional dopamine re-uptake inhibitors (such as cocaine or methylphenidate) would otherwise ineffectively target such a site on each specific transporter so affected 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.

References

  1. Rothman RB, Dersch CM, Ananthan S, Partilla JS (May 2009). "Studies of the biogenic amine transporters. 13. Identification of "agonist" and "antagonist" allosteric modulators of amphetamine-induced dopamine release". The Journal of Pharmacology and Experimental Therapeutics. 329 (2): 718–28. doi:10.1124/jpet.108.149088. PMC 2672863. PMID 19244097.
SoRI-20040
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