生物活性

• 靶点

  Adenosine Receptor A2A (rat) Ki:2.3nM

  Adenosine Receptor A2A (bovine) Ki:2nM

• 描述Adenosine modulates a variety of physiological functions acting via specific cell surface receptors which are divided into at least four subtypes: A1, A2a, A2b and A3. The A2a receptor subtype which is coupled to stimulation of adenylyl cyclase, is a high affinity receptor found in large amounts in the brain striatum. In the periphery, the A2a receptor is localized in different organs and tissues, including platelets, neutrophils and vascular smooth muscle cells ^[10]. SCH 58261 is an efficient and selective A2a adenosine receptor antagonist, with Ki values of 2.3 nM and 2 nM for rat A2a and bovine A2a, respectively, and displays 50- to 100-fold more selective for A2a receptor than A1, and shows no affinity for either the A3 adenosine receptor or other receptors at concentrations up to 1 mM in rat and bovine brain, respectively ^[11]. SCH 58261 (0 nM–10 µM; 7 days) decreases cell viability in a concentration-dependent in the NSCLC cell line H1975 ^[12]. It also antagonized competitively the effects induced by the A2a adenosine-selective agonist CGS 21680 in two functional assays, such as inhibition of rabbit platelet aggregation and porcine coronary artery relaxation ^[13]. SCH58261, systemically administered (0.01 mg/kg intraperitoneal. 1, 6 and 10 hours after spinal cord injury (SCI)), reduced demyelination and levels of TNF-α, Fas-L, PAR, Bax expression and activation of JNK mitogen-activated protein kinase (MAPK) 24 hours after SCI ^[14]. 6-OHDA (8 μg/rat, Intra-SNc) induced motor disorders of Parkinson's disease and increased elapsed time in the beam test (p<0.001). Injection of SCH-58261 (2 mg/kg, i.p.) attenuated elapsed time on beam (p<0.01 and p<0.001), which indicated administration of SCH-58261 can improve the 6-OHDA-induced bradykinesia and motor disturbance ^[15].

• 动物研究
  剂量	Mice: 0.1 mg/kg - 1 mg/kg[3] (i.p.), 2 mg/kg[4] (i.p.), 1 mg/kg - 10 mg/kg[5] (i.p.) Rat: 0.01 mg/kg - 1 mg/kg[6] (i.p.), 5 mg/kg[7] (i.p.); 0.5 mg/kg[8] (p.o.)
  给药途径	i.p., p.o.
  动物药代数据	Animal Rats[9] Dose 0.5 mg/kg Administration i.v. Cmax 109 ng/ml T1/2 26.7 min F 0.757