生物活性

• 靶点

  Adenosine Receptor A2 IC50:22nM

  Adenosine Receptor A1 IC50:3080nM

• 描述Adenosine is a neuromodulator maintaining adequate oxygen and energy supply throughout the body which is mediated by two specific cell-surface receptors known as A1 and A2. The 2 receptors are intense investigating targets for new drug developments in the treatment of hypertension and epilepsy^[6]. CGS 21680 is an adenosine receptors with IC50 values of 22 nM for A2 and 3.1 mM for A1 and with high affinity for brain striatal. CGS 21680 also showed 140-fold selective for A2 without effect on binding to 17 other adenosine receptor ligand sites. The drug increased coronary flow in a rat model^[2]. CGS 21680 could bind to A2 with high affinity (Kd = 15.5 nM), which was greatest in striatal membranes, consistent with a selective interaction in a pharmacological profile and high positive correlation between the pharmacological profile of adenosine ligands to inhibit the binding to A2 receptor^[7]. CGS 21680 was a weak agonist on A1 receptor mediated events in hippocampal slices and also not helpful of stimulating the formation of cAMP with an EC50 of only 110 nM, suggesting that CGS 21680 is selective at the high affinity adenosine for A2a receptor in striatum^[8].

• 动物研究
  剂量	Mice: 0.5 mg/kg[3] (i.p.) Rat: 0.5 mg/kg - 40 mg/kg[4] (s.c.)
  给药途径	i.p., s.c.
  动物药代数据	Animal Rats[5] Dose 0.3 mg/kg (i.v.) 3.0 mg/kg (p.o.) Administration i.v. p.o. F 140% (p.o.) B 558 ng/ml (i.v.) Tmax 13 min (p.o.) MRT 11 min (i.v.) A 6827 ng/ml (i.v.) CLp 0.83 L/kg/h (i.v.) T1/2β 15 min (i.v.) Cmax 94 ng/ml (p.o.) Vβ 0.27 L/kg (i.v.) T1/2α 1.8 min (i.v.) AUC 485 h·ng/ml (i.v.) 67 h·ng/ml (p.o.)