SKF-83566 (hydrobromide)

SKF-83566 hydrobromide is a potent, blood-brain permeable and orally active D1-like dopamine receptor (D1DR) antagonist and a weaker competitive antagonist at the vascular 5-HT₂ receptor (K_i=11 nM)^[1][3]. SKF-83566 is a competitive DAT (dopamine transporter) inhibitor with an IC₅₀ of 5.7 μM^[2]. SKF-83566 also shows selective inhibition for adenylyl cyclase 2 (AC₂) over AC₁ and AC₅ in the isolated rabbit thoracic aorta^[4]. SKF-83566 can be used for the research of parkinson’s disease and nicotine craving alleviation^[5]. In Vitro: SKF-83566 (0.1 μM-10 μM) causes a concentration-dependent increase in peak evoked extracellular DA concentration ([DA]_o) evoked by single-pulse stimulation, with a maximum 65% increase in peak evoked [DA]_o with 5 μM. The EC₅₀ value of this effect of SKF-83566 is 1.3 μM^[2].
SKF-83566 inhibited [³H]DA uptake with an IC₅₀ of 5.73 μM. Moreover, SKF-83566 more potently inhibits the binding of [³H]CFT, a cocaine analog, with an IC₅₀ of 0.51 μM in [³H]DA uptake and [³H]CFT binding studies.
Similarly, in LLc-PK-rDAT cell, SKF-83566 also inhibits [³H]CFT binding with an IC₅₀ of 0.77 μM in LLc-PK-rDAT cell membrane preparations^[2].
In Vivo: SKF 83566 hydrobromide (oral administration; 20 μg/mL; 7 days) alone has no effects on altering LTP (115%). However, combinnation of SKF 83566 and nicotine significantly blocks the enhancement of long-term synaptic potentiation (LTP) induced by pretreatment with nicotine (SKF 83566+nicotine+cocaine, 120%; nicotine+cocaine, 143%)^[1].