Zatebradine (UL-FS49)
(Synonyms: 扎替雷定,UL-FS-49 free base; UL-FS-49CL free base) 目录号 : GC32491
Zatebradine (UL-FS49) (UL-FS-49 (free base); UL-FS-49CL (free base)) 是一种有效的超极化激活环核苷酸门控 (HCN) 通道抑制剂，IC50 值为 1.96 μ ;M。
Cas No.:85175-67-3
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Zatebradine(UL-FS49) is a potent HCN channels antagonist, which decreased the heartbeat in a reversible manner; 92% inhibition of the hHCN1-mediated current at 10 uM.IC50 value: 10 uM(92% 92% inhibition of the hHCN1) [1]Target: hHCN channel antagonistThe pharmacological properties of hHCN1-mediated currents resembled those of native hyperpolarization-activated currents (I(h)), that is, blockade by Cs(+) (99% at 5 mm), ZD 7288 (98% at 100 microm) and zatebradine (92% at 10 microm) [1]. When voltage-clamp pulse trains were applied, cilobradine induced a use-dependent blockade of If that was stronger and faster than that with zatebradine. Recovery from blockade during prolonged hyperpolarization was significantly faster with zatebradine [2]. The selective HCN blocker zatebradine reduced the activity of oriens-lacunosum moleculare interneurons in wild-type but not HCN2(-/-) mice and decreased the frequency of spontaneous inhibitory currents in postsynaptic CA1 pyramidal cells [3].
[1]. Gill CH, et al. Characterization of the human HCN1 channel and its inhibition by capsazepine. Br J Pharmacol. 2004 Oct;143(3):411-21. [2]. Van Bogaert PP, et al. Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine. Eur J Pharmacol. 2003 Oct 8;478(2-3):161-71. [3]. Matt L, et al. HCN2 channels in local inhibitory interneurons constrain LTP in the hippocampal direct perforant path. Cell Mol Life Sci. 2011 Jan;68(1):125-37.
| Cas No. | 85175-67-3 | SDF | |
| 别名 | 扎替雷定,UL-FS-49 free base; UL-FS-49CL free base | ||
| Canonical SMILES | O=C1N(CCCN(CCC2=CC=C(OC)C(OC)=C2)C)CCC3=CC(OC)=C(OC)C=C3C1 | ||
| 分子式 | C26H36N2O5 | 分子量 | 456.57 |
| 溶解度 | DMSO : ≥ 50 mg/mL (109.51 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.1902 mL | 10.9512 mL | 21.9024 mL |
| 5 mM | 0.438 mL | 2.1902 mL | 4.3805 mL |
| 10 mM | 0.219 mL | 1.0951 mL | 2.1902 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine
Eur J Pharmacol 2003 Oct 8;478(2-3):161-71.PMID:14575801DOI:10.1016/j.ejphar.2003.08.083.
The action of the bradycardiac agents, cilobradine (DK-AH269) and Zatebradine (UL-FS49), on the cardiac pacemaker current (If) was investigated on short Purkinje fibres from sheep hearts, using the two-microelectrode voltage-clamp technique, and on isolated rabbit sino-atrial cells with the patch clamp technique. These drugs reduce dose dependently the amplitude of the If, without modifying either the voltage dependence or the kinetics of channel activation. When voltage-clamp pulse trains were applied, cilobradine induced a use-dependent blockade of If that was stronger and faster than that with zatebradine. Recovery from blockade during prolonged hyperpolarization was significantly faster with zatebradine. Presumably, both drugs block the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel by gaining access to a binding site within the open channel pore, and are removed from the blocking site by strong hyperpolarization with large inward If through the open channel. Cilobradine, compared to zatebradine blocks If more effectively and faster in both preparations. Consequently cilobradine strongly reduces the pacemaker diastolic depolarization rate and the cell's firing frequency.
Pharmacological influence of specific bradycardic agents on the pacemaker current of sheep cardiac Purkinje fibres. A comparison between three different molecules
Eur Heart J 1987 Dec;8 Suppl L:35-42.PMID:3451881DOI:10.1093/eurheartj/8.suppl_l.35.
The diastolic depolarization rate of isolated sheep Purkinje fibres was reduced in the presence of micromolar concentrations of the 'specific bradycardic agent' falipamil (AQ-A39) and its congener UL-FS49. Both drugs reduced the amount of pacemaker current, if, activated during the diastolic depolarization phase. The if activation curve was reduced in amplitude but not shifted. UL-FS49 was more effective compared to falipamil in causing this reduction of if amplitude at similar concentrations. The reduction of the if amplitude was presumably caused by a drug-induced decrease in if current conductance. This if current block showed use-dependence. With UL-FS49 less and less if was activated with every successive voltage clamp pulse of a train, with little recovery of if block after a rest interval. Use-dependent block was smaller with comparable falipamil concentrations but full recovery was observed after a rest interval. No use-dependent block was observed with alinidine, a drug which also causes reduction of if by shifting its activation range to more negative potentials. These results indicate that the reduction of pacemaker current observed with two different types of 'specific bradycardic agents' is obtained by different mechanisms.
Effects of tachycardia on regional wall motion in acute ischemic canine heart
Tohoku J Exp Med 2004 Jun;203(2):111-21.PMID:15212146DOI:10.1620/tjem.203.111.
Tachycardia accompanies the preload reduction. Our aim is to assess the effect of the heart rate change on wall motion in ischemic heart. In 8 dogs with occlusion of left anterior descending artery, we changed the heart rate (heart rate 90, 120, and 150 beats/minute) after using UL-FS49, a selective bradycardic agent, with atrial pacing. Preload was changed by inferior vena caval occlusion at a heart rate of 90 beats/minute. With either an increase in heart rate or an inferior vena caval occlusion, the end-diastolic length was decreased, but the end-diastolic length relationships between the non-ischemic and the ischemic region made different lines from those of the heart rate change and inferior vena caval occlusion. When increasing the heart rate, isovolumetric shortening was unchanged in the non-ischemic region with more expansion in the ischemic region. While inferior vena caval occlusion at a heart rate of 90 beats/minute, isovolumetric shortening was increased in the non-ischemic region, with more expansion in the ischemic region. Both in tachycardia and by the inferior vena caval occlusion, ejectional shortenings decreased in the non-ischemic and ischemic regions. Our results suggest that, in ischemic heart, tachycardia changes both in the end-diastolic length relationship between the non-ischemic and the ischemic region and at the isovolumetric contraction phase. The changes seem to be not only due to the inferior vena caval occlusion, but also due to tachycardia itself.
Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node
Cardiovasc Res 1995 Jun;29(6):867-78.PMID:7656291doi
Objective: The aim was to study the ionic basis of the chronotropic effects of bath applied acetylcholine and vagal stimulation on the rabbit sinoatrial node. Methods: The chronotropic effect of bath applied acetylcholine was measured in single cells and small multicellular preparations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatrial node. The roles of the hyperpolarisation activated current, i(f), the acetylcholine activated potassium current, iK,ACh, and the L-type calcium current, iCa, were investigated by blocking the currents with 1-2 mM Cs+ or 10(-6) M UL-FS49, 0.2-1.0 mM Ba2+, and 6 x 10(-6) M nifedipine, respectively. Results: Under control conditions, small multicellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, after block of acetylcholinesterase by eserine in small multicellular preparations the sensitivities of the two types of preparation were approximately the same. Block of i(f) either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on single cells or small multicellular preparations, whereas partial block of iK,ACh reduced it substantially. Similarly, block of i(f) did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of iK,ACh reduced it. The hyperpolarisation of the arrested sinoatrial node in response to vagal stimulation was also substantially reduced by block of iK,ACh. Partial block of iCa caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of spontaneous action potentials, and therefore did not mimic the effect of acetylcholine. Conclusions: The chronotropic effects of bath applied acetylcholine and vagal stimulation are not principally the result of a suppression of i(f) or iCa, whereas the activation of iK,ACh may play an important role.
Alinidine as a model of the mode of action of specific bradycardic agents on SA node activity
Eur Heart J 1987 Dec;8 Suppl L:25-33.PMID:3451880DOI:10.1093/eurheartj/8.suppl_l.25.
Three different bradycardic agents, alinidine, AQ-A39 and UL-FS49 increase the intrinsic cycle length of the isolated SA node preparation of the rabbit. This increase is mainly caused by a decrease in rate of diastolic depolarization. One of these agents, alinidine, was used to study the underlying ionic mechanism of the decrease in the diastolic depolarization rate in isolated cells and small cell clusters of the rabbit SA node. In these preparations alinidine slowed down the rate of spontaneous activity at higher concentrations (80 microM). At lower concentrations (10 microM) the decrease in rate of spontaneous activity was variable, but injection of a hyperpolarizing current slowed the spontaneous rate more in the presence of alinidine, indicating an increase in membrane resistance. In voltage clamp experiments we found that the main effect of alinidine was a block of the hyperpolarization activated current if. The block was potential dependent and was maximal in the potential range in which diastolic depolarization occurs. These results are discussed in relation to previous findings of others.