Table 2. Intrinsic activities and potencies of the five most active VS hits determined at the dopamine receptor subtype D2S by measuring the inhibition of forskolin-stimulated cAMP accumulation and recruitment of β-arrestin-2 after stimulation of the D2S receptor expressed in HEK cellsa.
Compound | Inhibition of forskolin-stimulated cAMP accumulation |
β-Arrestin recruitmentb |
||
---|---|---|---|---|
EC50 (nM) | Emax (%)c | EC50 (nM) | Emax (%)d | |
Delphinidin | N/A | 20% at 100 μM | N/A | <7 |
Fumigaclavine A | 250 | 27 | N/A | <7 |
Hordenine | 3700 | 76 | N/A | <7 |
Salsolinol | 630 | 21 | N/A | <7 |
Robenidine | N/A | <5 | N/A | <7 |
Dopamine | 0.97 | 100 | 420 | 96 |
aEC50 and Emax values were derived from mean curves based on 3–7 individual dose-response curves.
bD2S-mediated recruitment of β-arrestin-2 determined with the PathHunter assay.
cMaximum effect of forskolin-stimulated cAMP inhibition relative to the effect of quinpirole.
dMaximum effect of D2S-mediated β-arrestin recruitment relative to the maximum effect of quinpirole. N/A: EC50 values could not be analysed because of low corresponding Emax values.