Neu2000
(Synonyms: Salfaprodil free base; Neu2000) 目录号 : GC30860
Neu2000 (Salfaprodil free base) 是 N-甲基-D-天冬氨酸 (NMDA) 的 NR2B 选择性和非竞争性拮抗剂。
Cas No.:640290-67-1
Sample solution is provided at 25 µL, 10mM.
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Neu2000 is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist.
Neu2000 shows apparent neuroprotection against 300 μM N-methyl-D-aspartate (NMDA) at doses as low as 30 μM. Neu2000 does not protect cortical neurons against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- or kainate-mediates excitotoxicity. Neu2000 inhibits the electrophysiologic response of cultured cortical neurons to 300 μM NMDA in a concentration-dependent manner, indicating that the effect is mediated by a specific action at NMDA receptors. The Neu2000 dose-response has an IC50 of 35.38±5.94 μM and Hill's coefficient of 0.91 (n=8). Neu2000 (100 μM) significantly reduces the maximal NMDA response by 58.31±2.72% (n=5) and the EC50 values of NMDA from 18.88±1.85 to 9.92±0.17 μM (n=5, P<0.05)[1].
Pharmacokinetic analysis reveals that the half-life of Neu2000 is 1.42, 2.14, and 1.79 h following intraperitoneal administration of 10, 25, and 50 mg/kg, respectively. In addition, the Cmax (maximum plasma concentration) is calculated as 3.86, 18.73, and 52.83 μg/mL and the AUC (area under the curve) is determined to be 7.37, 55.15, and 96.77 μg/h/mL at the same respective doses. The levels of basal mitochondrial ROS are significantly elevated at 24 h post-surgery in both the vehicle-treated (4.1-fold, p<0.01) and Neu2000-treated (2.9-fold, p<0.01) groups compare to sham controls. The results of blood-brain barrier (BBB) test also reveals significant changes in open field locomotion in spinal cord-injured animals treated with Neu2000 compare to vehicle-treated animals. Single (p<0.05) or repeated (p<0.01) Neu2000 treatment results in a decreased swing to stance ratio compare to vehicle-treated animals. Repeated treatment with Neu2000 results in a 45.6% decrease (p<0.01) in overall lesion volume compare to vehicle treatment, while a single administration of Neu2000 results in a 36.8% decrease (p<0.05) in overall lesion volume[2].
[1]. Gwag BJ, et al. Marked prevention of ischemic brain injury by Neu2000, an NMDA antagonist and antioxidant derived from aspirin and sulfasalazine. J Cereb Blood Flow Metab. 2007 Jun;27(6):1142-51. [2]. Springer JE, et al. The functional and neuroprotective actions of Neu2000, a dual-acting pharmacological agent, in the treatment of acute spinal cord injury. J Neurotrauma. 2010 Jan;27(1):139-49.
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Cell experiment: |
Whole-cell voltage-clamp recordings are performed on primary cultured cortical neurons (11 to 14 DIV) at room temperature (18°C to 23°C). Whole-cell currents are recorded and analyzed using an amplifier. The 2 to 3-MΩ-resistance recording pipettes are filled with an internal solution containing 135 mM CsCl, 10 mM N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, 1.2 mM MgCl2, 4 mM ATP-Na2, 0.5 mM CaCl2, and 11 mM ethyleneglycol tetraacetate (pH adjusted to 7.3 with CsOH). The external solution is composed of 140 mM NaCl, 2 mM KCl, 2 mM CaCl2, 10 mM N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, and 0.01 mM glycine (pH adjusted to 7.3 to 7.4 with NaOH). N-methyl-D-aspartate and Neu2000 solutions are prepared by dissolving these chemicals in the external solutions, and they are applied to target neurons using a gravity-driven superfusion system with a linear array of 8 to 10 barrels. Graphing of data and dose-response analysis are performed and all data are presented as mean±s.e[1]. |
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Animal experiment: |
The pharmacokinetic profile of Neu2000 in normal rats is examined using intraperitoneal (ip) route of administration. Rats are anesthetized by ether inhalation and the femoral artery cannulated. Rats are placed into cages for 1 h and then receive injections (10, 25, or 50 mg/kg ip, n=6 per dose) of Neu2000 dissolved in sterile saline. Blood is collected from the femoral artery at 15, 30, 60, 120, 240, 480, and 1440 min following injection. Plasma aliquots of 50 μL are spiked with 100 μL of internal standard solution (Neu2000IS, 10 μg/mL in acetonitrile). After vortex mixing for 1 min, the samples are centrifuged at 12,000 g for 5 min. A total of 50 μL of the supernatant phase is separated and diluted with 50 μL of distilled water. Plasma concentrations relative to time are obtained using liquid chromatography-mass spectrometry[2]. |
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References: [1]. Gwag BJ, et al. Marked prevention of ischemic brain injury by Neu2000, an NMDA antagonist and antioxidant derived from aspirin and sulfasalazine. J Cereb Blood Flow Metab. 2007 Jun;27(6):1142-51. |
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| Cas No. | 640290-67-1 | SDF | |
| 别名 | Salfaprodil free base; Neu2000 | ||
| Canonical SMILES | OC(C1=C(O)C=CC(NCC2=C(C(F)=C(C(F)(F)F)C(F)=C2F)F)=C1)=O | ||
| 分子式 | C15H8F7NO3 | 分子量 | 383.22 |
| 溶解度 | DMSO : ≥ 112.5 mg/mL (293.57 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6095 mL | 13.0473 mL | 26.0947 mL |
| 5 mM | 0.5219 mL | 2.6095 mL | 5.2189 mL |
| 10 mM | 0.2609 mL | 1.3047 mL | 2.6095 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。
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet