SKF-83566

SKF-83566 is a blood-brain permeable and orally active antagonist of D1-like dopamine receptor and a weaker competitive 5-HT2 receptor antagonist with Ki of 11 nMSKF-83566 caused a concentration-dependent increase in peak single-pulse evoked extracellular DA concentration, with a maximum increase of 65% in 5 μM SKF-83566. This was accompanied by a concentration-dependent increase in extracellular DA concentration clearance time. Both effects were occluded by nomifensine (1 μM), a dopamine transporter (DAT) inhibitor, suggesting that SKF-83566 acted via the DAT. Tested this by examining [ (3) H]DA uptake into LLc-PK cells expressing rat DAT, and confirmed that SKF-83566 is a competitive DAT inhibitor with an IC (50) of 5.7 μM. Binding studies with [ (3) H]CFT, a cocaine analog, showed even more potent action of SKF-83566 at the DAT cocaine binding site (IC (50) = 0.51 μM) . The facilitation induced by nicotine and cocaine can be blocked by oral administration of the dopamine D1/D5 receptor antagonist (SKF 83566) .