TABLE 6

A summary of the evidence for allosteric modulation of DAT by SoRI compounds Cocaine competitively inhibits [3H]DA uptake (Zhu and Hexum, 1992) and DAT binding (Reith et al., 1992; Pariser et al., 2008).


Drug

[3H]DA Uptake

DAT Binding ([125I]RTI-55)

Effect on [125I]RTI-55 Dissociation from DAT

Effect on d-Amph-Induced DAT-Mediated Efflux of [3H]MPP+

Effect on d-Amph-Induced DAT-Mediated DA Release
Cocaine “Normal” competitive inhibitor Normal competitive inhibitor No effecta Slows d-Amph-induced efflux by changing apparent rate constants Competitive inhibitor
SoRI-9804 Partial inhibitor decreases Vmaxa Partial inhibitor decreases Bmaxa Slowed dissociation ratea Slows d-Amph-induced efflux without changing apparent rate constants Partial inhibitor “agonist-like”
SoRI-20040 Partial inhibitor decreases Vmax Partial inhibitor decreases Bmax Slowed dissociation rate Not determined; direct effects at high concentrations Partial inhibitor agonist-like
SoRI-20041 Partial inhibitor decreases Vmax Partial inhibitor decreases Bmax Slowed dissociation rate Not determined; direct effects at high concentrations No effect “antagonist-like”
SoRI-2827
Partial inhibitor decreases Vmax, but less so than SoRI-20040 and SoRI-20041
Partial inhibitor decreases Bmax
No effect on dissociation rate
Not studied; nonspecific effects
Not studied; nonspecific effects
  • a Unpublished data