SoRI-20041
Identifiers
  • 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)
  • c2ccccc2C(c3ccccc3)CCNc(nc4-c5ccccc5)c1ccccc1n4
  • 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

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]

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. ^ a b c 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
SoRI-20040