(+)-PD 128907 hydrochloride

(+)-PD 128907 hydrochloride is a selective dopamine D₂/D₃ receptor agonist, with K_is of 1.7, 0.84 nM for human and rat D₃ receptors, 179, 770 n M for human and rat D₃ receptors, respectively. IC50 & Target: Ki: 1.7 nM (human D₃ receptor), 0.84 nM (rat D₃ receptor), 179 nM (human D₂ receptor), 770 nM (rat D₂ receptor)^[1][2]. In Vitro: (+)-PD 128907 displaced [³H]spiperone binding from dopamine D₃ receptors (K_i human=1.7 nM and rat=0.84 nM) with >100-fold and 900-fold selectivity over the human (K_i=179 nM) and rat (K_i=770 nM) dopamine D₂ receptor^[1][2]. In Vivo: (+)-PD 128907 significantly decreases dialysate DA levels in D₃ knock out mice. The IC₂₅ values are 61 nM and 1327 nM, respectively, for wild type and D₃knock out mice. The ratio of the IC₂₅ values shows that (+)-PD 128907 is 22 times more potent in decreasing dialysate DA levels in wild type as compared to mice lacking the D₃ receptor. The D3 agonist evokes a dose related decrease in dialysate DA in wild type mice. Post-hoc analysis shows that all doses tested (0.03, 0.1 and 0.3 mg/kg) significantly inhibit dialysate DA. The IC₂₅ values are 0.05 and 0.44 mg/kg for wild type and knock out mice, respectively, indicating that systemically administered (+)-PD 128907 is 9 times more potent in decreasing dialysate DA in the ventral striatum of wild type as compared to D₃ knock out mice. Doses of 1 mg/kg or higher of (+)-PD 128907 markedly inhibits dialysate DA in both wild type and D₃ knock out mice^[3].