SKF-83566 (hydrobromide)

SKF-83566 hydrobromide is an orally active, blood-brain barrier-permeable D1/D5 dopamine receptor antagonist with a K_i value of approximately 0.4-0.56 nM. SKF-83566 hydrobromide modulates locomotor behavior and spatial memory by blocking D1 receptors and inhibits glioblastoma progression by targeting the DRD1/c-Myc/UHRF1 pathway. SKF-83566 hydrobromide acts as an inhibitor of the dopamine transporter (DAT) and adenylyl cyclase 2 (AC2). SKF-83566 hydrobromide competitively binds to DAT to inhibit dopamine reuptake and non-competitively inhibits AC2 activity, thereby reducing cAMP accumulation. SKF-83566 hydrobromide is used in research areas such as dopaminergic system mechanisms, learning and memory, targeted intervention for glioblastoma, AC2 pathophysiology, antiparasitic drug screening, and synaptic plasticity (the "gating effect")^{[1][2][3][4][5][6][7][8]}. In Vitro:SKF-83566 (5 μM; 5 min pre-incubation) hydrobromide acts as a competitive inhibitor of DAT in LLc-PK cells expressing rat dopamine transporter (rDAT), with an IC₅₀ value of 5.73 µM^[2].
SKF-83566 (10 pM-1 mM; 15 min) hydrobromide inhibits [³H]CFT binding in intact LLc-PK-rDAT cells and cell membrane preparations, with IC₅₀ values of 0.51 μM and 0.77 μM, respectively^[2].
SKF-83566 (10-30 μM; 30 min pre-incubation + 1 h co-stimulation) hydrobromide potently and completely inhibits the suppression of cAMP accumulation induced by PMA (HY-18739), PGE2 (HY-101952) and Forskolin (HY-15371) in HEK-hAC2 cells, with an IC₅₀ value ranging from 10 to 21 μM^[7].
SKF-83566 (75-200 µM; pre-incubated for 10 min) hydrobromide non-competitively inhibits AC2 activity in Sf9 insect cell membranes expressing AC2^[7].
SKF-83566 (pre-incubated for 30 min, stimulated for 1 h) hydrobromide inhibits Forskolin-stimulated cAMP accumulation in mouse C2C12 skeletal muscle myotubes, with an IC₅₀ of 15 μM^[7].
SKF-83566 (30 µM; pre-incubated for 20 min, stimulated for 1 h) hydrobromide inhibits Forskolin-stimulated IL-6 mRNA expression in human bronchial smooth muscle cells (hBSMCs)^[7].
SKF-83566 (1-100 μM; pre-incubation for 10 min, followed by stimulation with bile acid for 2 h) hydrobromide almost completely inhibits bile acid-induced chemotaxis of adult Clonorchis sinensis in vitro^[3].
SKF-83566 (50-100 μM; 14 days) hydrobromide dose-dependently inhibits the self-renewal and tumorsphere-forming ability of P3, BG5 and BG7 glioma stem cells^[6].
SKF-83566 (0-400 µM; 48-72 h) hydrobromide inhibits the viability of U251, LN18, LN229, A172, P3, BG5 and BG7 cells, with IC₅₀ values ranging from 119.4 to 381.7 μM, which are significantly lower than the IC₅₀ of 986 μM measured in normal human astrocytes^[6].
SKF-83566 (100 µM; 72-96 h) hydrobromide significantly inhibits tumor invasion in human GSCs (P3, BG5, BG7) co-cultured with brain organoids, and exerts the same effect in the 3D tumor sphere invasion model^[6].
SKF-83566 (50-100 μM) hydrobromide dose-dependently downregulates the mRNA and protein expression of c-Myc and UHRF1 in P3, BG5 and BG7 glioma stem cells, but exerts no such effect on normal human astrocytes^[6].
SKF-83566 (50-100 µM) hydrobromide induces G0/G1 cell cycle arrest and promotes apoptosis in human GSCs (P3, BG5, BG7)^[6]. In Vivo:SKF-83566 (0.04-0.2 mg/kg; systemic administration; single dose; administered once 30 min prior to agonist treatment) hydrobromide exerts a dose-dependent effect on blocking the stereotyped behaviors induced by agonists (Apomorphine (HY-12723) and RU24213 (HY-136786)) in male rats^[1].
SKF-83566 (0.02-0.2 mg/kg; i.m.; once daily for 3 consecutive days) hydrobromide does not significantly alter the ability to learn the eccentric spatial maze in young and aged rhesus monkeys^[4].
SKF-83566 (10-100 µg/kg; i.p.; single administration 15 min prior to memory testing or ghrelin injection) hydrobromide reverses ghrelin-induced memory enhancement in male rat models, but has no effect on its orexigenic action ^[5].
SKF-83566 (20 mg/mL; p.o.; administered consecutively for 7 days) hydrobromide blocks the priming effect of nicotine on cocaine-induced long-term potentiation (LTP) in the hippocampal dentate gyrus (DG) in male mouse models^[6].
SKF-83566 (20 mg/kg/day; i.p.; once daily, administered continuously until symptom onset followed by euthanasia) hydrobromide inhibits tumor growth and invasion, reduces the expression of key proteins, and prolongs overall survival in athymic nude mice bearing intracranial orthotopic xenograft tumors of GSC^[6].