| 名稱 | Capadenoson |
| 描述 | Capadenoson (BAY 68-4986) is a selective adenosine-A1 receptor agonist. |
| 激酶實驗 | Membranes from the human cortex are prepared. [35S]GTPγS binding is measured. Briefly, 5 μg of membrane protein is incubated in a total volume of 160 μL for 2 hr at 25°C in a shaking water bath. [35S]GTPγS binding in control incubations and in the presence of Capadenoson showed a linear time course up to this incubation time. Binding buffer contained 50 mM Tris/HCl, pH 7.4, 2 mM triethanolamine, 1 mM EDTA, 5 mM MgCl2, 10 μM GDP, 1 mM dithiothreitol, 100 mM NaCl, 0.2 units/mL adenosine deaminase, 0.2 nM [35S]GTPγS, and 0.5% bovine serum albumin. Non-specific binding is determined in the presence of 10 μM GTPγS. Incubations are terminated through filtration of the samples over multiscreen FB glass fiber filters followed by two washes with binding buffer. The filters are dried, coated with scintillator and counted for radioactivity. Binding curves of [35S]GTPγS are analyzed by nonlinear regression using GraphPad Prism. |
| 動物實驗 | A total of 14 Wistar rats and 18 SHR (bodyweight 200-50 g, all-female) underwent experiments to evaluate the exocytotic, stimulation-induced NE release during electrical field stimulation. Rats are killed by an injection of pentobarbital i.p. (0.5 mL/100 mg body weight), and hearts are rapidly excised, and placed in ice-cold Krebs-Henseleit solution (KHL). They are quickly mounted on a Langendorff apparatus for retrograde perfusion with KHL. Perfusion rate is kept constant at 10 mL/min, the temperature is adjusted to 37°C, and the pH to 7.4 through bubbling with 5% CO2/95% O2. Via an inflow line desipramine at a concentration of 10?7 M is added to the perfusion buffer. After an equilibration period of 20 minutes, electrical field stimulation is commenced via two metal paddles adjacent to both sides of the beating heart for 1 minute (5V, 6 Hz). We collected the efflux in plastic tubes the minute before, during, and 3 minutes after the stimulation. These are rapidly frozen in liquid nitrogen and stored at ?20°C till analysis. The NE release is calculated as the cumulative release induced by electrical stimulation. After the first stimulation (S1), the study drug Capadenoson at concentrations of 30 μg/L (6×10^?8 M) or 300 μg/L(6×10^?7 M), or CCPA (10^?6 M), respectively, are added via separate perfusion lines for 30 minutes. After this time a second stimulation (S2) is executed to determine the effect of the drugs on NE release compared to the first stimulation. The effect of each pharmacological intervention is analyzed by calculating the ratio of NE release induced by the second and first stimulation (S2/S1 ratio). |
| 體外活性 | 為了進一步闡明Capadenson的藥理特性，采用標(biāo)準(zhǔn)全A1激動劑CCPA和A1拮抗劑DPCPX進行GTP轉(zhuǎn)移試驗。在大鼠皮質(zhì)腦膜結(jié)合實驗中，CCPA顯示出4.2 nM的Ki值。在1 mM GTP存在下，該Ki值轉(zhuǎn)變?yōu)?4 nM，因此，CCPA的GTP轉(zhuǎn)移值為15。DPCPX在GTP存在與否下顯示出幾乎相同的Ki值，其GTP轉(zhuǎn)移值為1。Capadenson在結(jié)合實驗中顯示出24 nM的Ki值，在1 mM GTP存在下，該Ki值轉(zhuǎn)變?yōu)?16 nM，從而得出Capadenson的GTP轉(zhuǎn)移值為5。 |
| 體內(nèi)活性 | 在活體實驗中，Wistar大鼠和SHR在進行應(yīng)激測試（體力限制）的前5天預(yù)先用Capadenoson（0.15 mg/kg）處理。在第5天，進行為期2小時的應(yīng)激測試。在限制應(yīng)激測試前的5天內(nèi)，Capadenoson的血漿濃度在服藥后3小時測量，保持恒定，第4天和第5天的平均濃度分別為7.63 μg/L。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 70 mg/mL (134.61 mM)
H2O : Insoluble
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| 關(guān)鍵字 | Adenosine Receptor | Capadenoson | P1 receptor | Inhibitor | inhibit |
| 相關(guān)產(chǎn)品 | Adenosine 5'-monophosphate monohydrate | Inosine | Istradefylline | Adenosine antagonist-1 | Theophylline | Acefylline | Theobromine | Aminophylline | Theophylline monohydrate | Diphylline | FK-453 | Doxofylline |
| 相關(guān)庫 | 神經(jīng)保護化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | GPCR靶點分子庫 | 膜蛋白靶向化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |