生物活性

• 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 ^[6]. ZM 241385 is a novel non-xanthine adenosine receptor antagonist with selectivity for the A2a receptor subtype ^[7]. In rat phaeochromocytoma cell membranes, ZM 241385 displaced binding of tritiated 5'-N-ethylcarboxamidoadenosine (NECA) with a pIC50 of 9.52. In guinea-pig isolated Langendorff hearts, ZM 241385 antagonized vasodilatation of the coronary bed produced by 2-chloroadenosine (2-CADO) and 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680) with pA2 values of 8.57 and 9.02 respectively. It also antagonized the bradycardic action of 2-CADO in guinea-pig atria with a pA2 of 5.95 ^[7]. In the CA1 area of the rat hippocampus, which is the most sensitive region to ischemia, ZM241385, delay the appearance of anoxic depolarization (AD), protect from the synaptic activity depression brought about by a severe (7 min) OGD period, and protect CA1 neuron and astrocyte from injury ^[8].

• 动物研究
  剂量	Rat: 10 mg/kg (i.v.); 3 mg/kg - 10 mg/kg[3] (p.o.) Mice: 50 mg/kg[4] (i.p.)
  给药途径	i.v., p.o., i.p.
  动物药代数据	Animal Rats[5] Dose 5 mg/kg Administration i.v. or p.o. F 6.57 ± 0.26% (p.o.) T1/2 89.42 ± 18.14 min (i.v.) 144.48 ± 20.87 min (p.o.) AUC 100,446.26 ± 41,828.36 ng·min/ml (i.v.) 6599.69 ± 1232.90 ng·min/ml (p.o.) CL 54.57 ± 18.34 ml/min/kg (i.v.) Cmax 4458.03 ± 282.51 ng/ml (i.v.) 58.29 ± 12.64 ng/ml (p.o.) Vss 1880.38 ± 618.10 L/kg (i.v.)