Perzinfotel
(Synonyms: EAA-090) 目录号 : GC36876
Perzinfotel (EAA-090) 是一种有效选择性的，竞争性的 NMDA 受体拮抗剂，具有神经保护作用。Perzinfotel (EAA-090) 对谷氨酸位点显示出高亲和力 (IC50=30 nM)。
Cas No.:144912-63-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Perzinfotel (EAA-090) is a potent, selective, and competitive NMDA receptor antagonist with neuroprotective effects. Perzinfotel (EAA-090) shows high affinity (IC50=30 nM) for the glutamate site[1][2]. NMDA receptor[1]
Perzinfotel blocks NMDA-induced currents with an IC50 of 0.48 μM and glutamate-induced neurotoxicity with an IC50 of 1.6 μM[1].
[1]. Brandt MR, et al. Effects of the N-methyl-D-aspartate receptor antagonist perzinfotel [EAA-090; [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid] on chemically induced thermal hypersensitivity. J Pharmacol Exp Ther. 2005 Jun;313(3):1379-86. [2]. Kinney WA, et al. Design and synthesis of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)-ethyl]phosphonic acid(EAA-090), a potent N-methyl-D-aspartate antagonist, via the use of 3-cyclobutene-1,2-dione as an achiral alpha-amino acid bioisostere. J Med Chem. 1998 Jan 15;41(2):236-46.
| Cas No. | 144912-63-0 | SDF | |
| 别名 | EAA-090 | ||
| Canonical SMILES | O=C(C1=C2NCCCN1CCP(O)(O)=O)C2=O | ||
| 分子式 | C9H13N2O5P | 分子量 | 260.18 |
| 溶解度 | DMSO : 20.83 mg/mL (80.06 mM; Need ultrasonic); H2O : 5.88 mg/mL (22.60 mM; ultrasonic and warming and heat to 60°C) | 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 | 3.8435 mL | 19.2175 mL | 38.4349 mL |
| 5 mM | 0.7687 mL | 3.8435 mL | 7.687 mL |
| 10 mM | 0.3843 mL | 1.9217 mL | 3.8435 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。
Effects of Perzinfotel on the minimum alveolar concentration of isoflurane in dogs when administered as a preanesthetic via various routes or in combination with butorphanol
Am J Vet Res 2010 Jun;71(6):604-9.PMID:20513173DOI:10.2460/ajvr.71.6.604.
Objective: To determine the anesthetic-sparing effects of Perzinfotel when administered as a preanesthetic via IV, IM, or SC routes or IM in combination with butorphanol. Animals: 6 healthy sexually intact Beagles (4 males and 2 females; age, 18.5 to 31 months; body weight, 9.8 to 12.4 kg). Procedures: After administration of a placebo, Perzinfotel (10 to 30 mg/kg), or a perzinfotel-butorphanol combination, anesthesia was induced in dogs with propofol and maintained with isoflurane in oxygen. The following variables were continuously monitored: bispectral index; heart rate; systolic, diastolic, and mean arterial blood pressures; end-tidal concentration of isoflurane; end-tidal partial pressure of CO(2); oxygen saturation as measured by pulse oximetry; rectal temperature; and inspiration and expiration concentrations of isoflurane. A noxious stimulation protocol was used, and the minimum alveolar concentration (MAC) was determined twice during anesthesia. Results: IV, IM, and SC administration of Perzinfotel alone decreased the mean isoflurane MAC values by 32% to 44% and significantly increased bispectral index values. A dose of 30 mg of Perzinfotel/kg IM resulted in significant increases in heart rate and diastolic arterial blood pressure. The greatest MAC reduction (59%) was obtained with a combination of 20 mg of Perzinfotel/kg IM and 0.2 mg of butorphanol/kg IM, whereas administration of butorphanol alone yielded a 15% reduction in the isoflurane MAC. Conclusions and clinical relevance: SC, IM, or IV administration of Perzinfotel prior to induction of isoflurane anesthesia improved anesthetic safety by reducing inhalant anesthetic requirements in healthy dogs.
Effects of Perzinfotel on the minimum alveolar concentration of isoflurane in dogs
Am J Vet Res 2007 Dec;68(12):1294-9.PMID:18052733DOI:10.2460/ajvr.68.12.1294.
Objective: To determine the effect of IV administration of Perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy sexually intact male Beagles. Procedures: Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of Perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO(2)) were monitored throughout anesthesia. Results: Isoflurane MAC was 1.32 +/- 0.14%. Intravenous administration of Perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of Perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO(2) did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of Perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg. Conclusions and clinical relevance: IV administration of Perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.
Effects of intravenous administration of Perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs
Am J Vet Res 2009 Dec;70(12):1459-64.PMID:19951116DOI:10.2460/ajvr.70.12.1459.
OBJECTIVE-To determine the effects of IV administration of Perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), Perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of Perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of Perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when Perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of Perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.
Effects of Perzinfotel, butorphanol tartrate, and a butorphanol-perzinfotel combination on the minimum alveolar concentration of isoflurane in cats
Am J Vet Res 2010 Nov;71(11):1270-6.PMID:21034317DOI:10.2460/ajvr.71.11.1270.
Objective: To determine the effects of Perzinfotel, butorphanol, and their combination on the minimal alveolar concentration (MAC) of isoflurane in cats. Animals: 7 healthy sexually intact cats (4 males and 3 females), aged 12 to 17 months and weighing 2.8 to 4.6 kg. Procedures: In a crossover design, saline (0.9% NaCl) solution, Perzinfotel (2.5 to 15 mg/kg; IV, IM, and SC), butorphanol tartrate (0.2 mg/kg, IM), or a combination of 5 mg of Perzinfotel/kg and 2 mg of butorphanol tartrate/kg (both IM) was administered to 6 cats before 7 separate episodes of anesthesia with isoflurane in oxygen. Heart rate, arterial blood pressure, bispectral index (BIS), and inspiration and expiration concentrations of isoflurane were continuously monitored. The isoflurane MAC was determined twice during anesthesia. Results: IV, IM, and SC administration of Perzinfotel at 2.5 to 15 mg/kg resulted in a significant decrease in mean isoflurane MAC by 43.3% to 68.0%. The BIS significantly increased after Perzinfotel administration via the same routes at 2.5 to 15 mg/kg and after perzinfotel-butorphanol administration IM. Blood pressure was significantly higher after Perzinfotel was administered at 5 mg/kg, IM; 10 mg/kg, IV; and 10 mg/kg, SC than after saline solution administration. Conclusions and clinical relevance: Perzinfotel administration decreased the isoflurane MAC and increased several BIS and blood pressure values in anesthetized cats. Administration of Perzinfotel prior to isoflurane anesthesia may improve anesthetic safety by reducing inhalant anesthetic requirements and improving cardiovascular function during anesthesia.
Prodrugs of Perzinfotel with improved oral bioavailability
J Med Chem 2009 Feb 12;52(3):771-8.PMID:19146418DOI:10.1021/jm8011799.
Previous studies with Perzinfotel (1), a potent, selective, competitive NMDA receptor antagonist, showed it to be efficacious in inflammatory and neuropathic pain models. To increase the low oral bioavailability of 1 (3-5%), prodrug derivatives (3a-h) were synthesized and evaluated. The oxymethylene-spaced diphenyl analogue 3a demonstrated good stability at acidic and neutral pH, as well as in simulated gastric fluid. In rat plasma, 3a was rapidly converted to 1 via 2a. Pharmacokinetic studies indicated that the amount of systemic exposure of 1 produced by a 10 mg/kg oral dose of 3a was 2.5-fold greater than that produced by a 30 mg/kg oral dose of 1. Consistent with these results, 3a was significantly more potent and had a longer duration of activity than 1 following oral administration in a rodent model of inflammatory pain. Taken together, these results demonstrate that an oxymethylene-spaced prodrug approach increased the bioavailability of 1.