生物活性

• 描述Adenosine receptor plays important roles in the fertilization process, kidney function and ethanol intoxication as well as angina and heart failure, thus becoming a promising target in clinic. Capadenoson is a selective agonist of adenosine receptor showing Ki of 4.2 nM when binding on rat cortical brain membranes. Capadenoson could also decrease neurotransmitter norepinephrine (NE) releasing at very low concentration. At a concentration of 0.15 mg/kg, capadenoson treatment led to 15% increasing in heart rate during stress^[1]. In another investigation, sixty-two male patients with stable angina were studied and treated with capadenoson at oral doses of 1, 2.5, 5, 10 and 20 mg respectively and placebo group was settled as the control. In 10 mg group heart rate was reduced by 12.2 bpm which was 6.8 bpm in 20 mg group in the primary efficacy analysis. Mean HR reduction after dosing for 24 h were 9.9 and 10.3 bpm for 10 mg and 20 mg respectively. In terms of safety, 32% of these patients had suffered at least one adverse events (AE), which was 36%, 30%, 20% and 30% in the control, the 5 mg, 10 mg and 20 mg respevtively, suggesting the 10 mg dose could be the best concentration to reduce heart rate in clinic^[2][3].
• 作用机制Capadenoson binding to the adenosine-A1 receptor that can inhibit adenylcyclase and decrease cAMP production by activating A1-coupled Gi protein^[3] .

• 动物研究
  剂量	Rat: 0.03 mg/kg - 0.3 mg/kg[4] (i.v.); 1 mg/kg, 2 mg/kg[5] (i.p.)
  给药途径	i.v., i.p.
  动物药代数据	Animal Rats[6] Dogs[6] Monkeys[6] Dose 0.5 mg/kg (i.v.) 1 mg/kg (p.o.) 0.3 mg/kg (i.v.) 1 mg/kg (p.o.) 0.3 mg/kg (i.v.) 1 mg/kg (p.o.) Administration i.v. p.o. i.v. p.o. i.v. p.o. F 57% (p.o.) 21% (p.o.) 60% (p.o.) CLb 1.4 L/h/kg (i.v.) 1.2 L/h/kg (i.v.) 0.21 L/h/kg (i.v.) T1/2 8.4 h 2.4 h 9.8 h Vss 10 L/kg (i.v.) 2.3 L/kg 2.7 L/kg