Pralidoxime chloride (2-PAM chloride)
(Synonyms: 氯解磷定,2-PAM chloride) 目录号 : GC33684
An AChE reactivator
Cas No.:51-15-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pralidoxime reactivates acetylcholinesterase (AChE) that has been deactivated by binding of organophosphates to its esteratic site.1 Pralidoxime binds to the anionic site of AChE and displaces the phosphate from the esteratic site through formation of phosphate-pralidoxime conjugates. It reactivates paraoxon- and diisopropyl fluorophosphate-inactivated human red blood cell (RBC) AChE with IC50 shifts of 0.3 and 0.8 nM per μM of pralidoxime, respectively.2,3 At a concentration of 10 μM, it reactivates human RBC AChE that has been inactivated by chlorpyrifos , diazinon , and malathion by 17, 61, and 36%, respectively.4 Pralidoxime binds to sarin-bound hAChE (Kd = 25.72 μM) and inhibits sarin-induced AChE deactivation (IC50 = 1.21 mM) in hemoglobin-free erythrocyte ghosts.5 Formulations containing pralidoxime have been used to treat organophosphate poisoning.1
1.Jokanovi?, M., and Stojiljkovi?, M.P.Current understanding of the application of pyridinium oximes as cholinesterase reactivators in treatment of organophosphate poisoningEur. J. Pharmacol.553(1-3)10-17(2006) 2.Petroianu, G.A., Arafat, K., Kuca, K., et al.Five oximes (K-27, K-33, K-48, BI-6 and methoxime) in comparison with pralidoxime: In vitro reactivation of red blood cell acetylcholinesterase inhibited by paraoxonJ. Appl. Toxicol.26(1)64-71(2006) 3.Lorke, D.E., Hasan, M.Y., Arafat, K., et al.In vitro oxime protection of human red blood cell acetylcholinesterase inhibited by diisopropyl-fluorophosphateJ. Appl. Toxicol.28(4)422-429(2008) 4.Costa, M.D., Freitas, M.L., Soares, F.A., et al.Potential of two new oximes in reactivate human acetylcholinesterase and butyrylcholinesterase inhibited by organophosphate compounds: An in vitro studyToxicol. In Vitro25(8)2120-2123(2011) 5.Karade, H.N., Raviraju, G., Acharya, B.N., et al.Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE)Bioorg. Med. Chem.24(18)4171-4176(2016)
| Cas No. | 51-15-0 | SDF | |
| 别名 | 氯解磷定,2-PAM chloride | ||
| Canonical SMILES | C[N+]1=CC=CC=C1/C=N/O.[Cl-] | ||
| 分子式 | C7H9ClN2O | 分子量 | 172.61 |
| 溶解度 | DMSO : 11.33 mg/mL (65.64 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 | 5.7934 mL | 28.967 mL | 57.9341 mL |
| 5 mM | 1.1587 mL | 5.7934 mL | 11.5868 mL |
| 10 mM | 0.5793 mL | 2.8967 mL | 5.7934 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。
Oxidative mechanisms for the biotransformation of 1-methyl-1,6-dihydropyridine-2-carbaldoxime to Pralidoxime chloride
Life Sci 2011 Dec 19;89(25-26):911-7.PMID:21989207DOI:10.1016/j.lfs.2011.09.019.
Aims: Due to Pralidoxime chloride's (2-PAM) positive charge, it's penetration through the blood brain barrier (BBB) and reactivation of organophosphate (OP) inhibited central nervous system (CNS) acetylcholinesterase (AChE) is poor. The results of CNS inhibited AChE are seizures. Pro-2-PAM (1-methyl-1,6-dihydropyridine-2-carbaldoxime), a pro-drug of 2-PAM, due to higher hydrophobicity, penetrates the BBB better but must be oxidized to 2-PAM, the active form of the oxime to reactivate CNS AChE in order to abrogate seizures. In this study, we characterize the in vivo mechanism of pro-2-PAM oxidation. Main methods: A high pressure liquid chromatography (HPLC) assay was developed to quantify the conversion of pro-2-PAM to 2-PAM. NADPH oxidase activity was measured by a photo-luminescence assay using lucigenin substrate. Upon analysis, the rate of NADPH induced oxidation suggested that an alternate mechanism may be involved. Therefore, various enzyme co-factors of oxidation-reduction enzyme systems were evaluated, including nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide phosphate (NADP), flavin adenine dinucleotide (FAD), riboflavin 5'-phosphate (FMN), and riboflavin. Next, a spectrophotometric assay was developed to measure the conversion of pro-2-PAM to 2-PAM in the presence of riboflavin. Key findings: In guinea pig brain homogenate, diphenyleneiodonium (DPI), a specific NADPH oxidase inhibitor, reduced pro-2-PAM to 2-PAM conversion to less than 25%. In contrast, riboflavin, FAD, and FMN rapidly oxidized all pro-2-PAM to 2-PAM in an in vitro assay. Riboflavin oxidized pro-2-PAM reactivated diisopropylfluorophosphate (DFP) inhibited AChE. Significance: The present study shows that pro-2-PAM was rapidly oxidized by riboflavin to 2-PAM, which reactivated organophosphate (OP)-inhibited AChE.
A comparison of cholinergic effects of HI-6 and pralidoxime-2-chloride (2-PAM) in soman poisoning
Toxicol Lett 1991 Feb;55(2):131-47.PMID:1998202DOI:10.1016/0378-4274(91)90128-s.
The effects of HI-6 and Pralidoxime chloride (2-PAM) on soman-induced lethality, time to death and several cholinergic parameters in rats were compared to understand the beneficial action of HI-6. Treatment with atropine sulfate (ATS) or HI-6 alone protected against 1.2 and 2.5 LD50s of soman respectively, whereas 2-PAM or methylated atropine (AMN) alone afforded no protection. Addition of ATS, but not AMN, to HI-6-treated rats enhanced the protection from 2.5 to 5.5 LD50s. HI-6 increased the time-to-death, while 2-PAM had no effect; a combination of HI-6 and ATS provided the most significant increase in time-to-death. Cholinesterase (ChE) activity was not altered in any tissue by ATS, HI-6 or 2-PAM treatment individually, but was markedly inhibited in all tissues by 100 micrograms/kg of soman. In soman-poisoned rats, the HI-6, but not the 2-PAM, group had significantly higher levels of ChE in blood and other peripheral tissues than did the group given soman alone. Neither HI-6 nor 2-PAM affected soman-inhibited ChE in the brain. Additional ATS treatment had no effect on ChE activity. HI-6 and 2-PAM neither modified baseline brain acetylcholine (ACh) or choline (Ch) levels nor protected against soman-induced ACh or Ch elevation. 2-PAM exhibited a 4-fold more potent in vitro inhibition of 3H-quinuclidinyl benzilate (3H-QNB) binding and sodium-dependent high-affinity Ch uptake (HACU) than did HI-6 in brain tissues. The findings that 2-PAM is a more potent in vitro inhibitor of muscarinic receptor binding and HACU than HI-6, and yet neither elevates ChE activity in the periphery nor protects rats against soman poisoning, indicate the importance of higher ChE activity in the periphery of HI-6-treated rats. Maintenance by HI-6 of a certain amount of active ChE in the periphery appears to be important for survival after soman exposure.
Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH2(Fe)
ACS Appl Mater Interfaces 2023 Mar 15;15(10):12631-12642.PMID:36867458DOI:10.1021/acsami.2c18929.
It is very important to establish a sustained-release Pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH2(Fe) nanoparticles with a size of ∼100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH2(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
Therapeutic dosing of Pralidoxime chloride
Drug Intell Clin Pharm 1987 Jul-Aug;21(7-8):590-3.PMID:3301250DOI:10.1177/1060028087021007-804.
Pralidoxime chloride is a useful agent in the treatment of organophosphate poisoning. Poisindex, a widely used poisoning treatment resource, recommends dosing Pralidoxime chloride as an intermittent iv infusion every 8-12 hours, whereas other authors have used continuous iv infusion with good results. Available animal data suggest that a serum concentration of 4 micrograms/ml may be a minimal level to protect against the toxic effects of organophosphates. Pharmacokinetic simulations, based on parameters obtained from healthy nonpoisoned subjects, show that pralidoxime levels fall rapidly to less than 4 micrograms/ml within 1.5-2 hours after a 1-g iv bolus. Continuous iv infusion (0.5 g/h) maintains pralidoxime levels greater than 4 micrograms/ml throughout the length of infusion. We conclude that continuous iv infusion of Pralidoxime chloride may be the preferred method of administration in patients with acute organophosphate poisoning. Clinical trials will be necessary to document the effectiveness of this regimen.
Nanoparticle-Delivered 2-PAM for Rat Brain Protection against Paraoxon Central Toxicity
ACS Appl Mater Interfaces 2017 May 24;9(20):16922-16932.PMID:28504886DOI:10.1021/acsami.7b04163.
Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, Pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30.8 ± 1%). Drug-loaded particles had a mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54 to -15 mV). These properties contribute to improve long-term stability of 2-PAM-SLNs when stored both at room temperature (22 °C) and at 4 °C, as well as to longer circulation time in the bloodstream compared to free 2-PAM. Paraoxon-poisoned rats (2 × LD50) were treated with 2-PAM-loaded SLNs at a dose of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our results confirm the potential use of SLNs loaded with positively charged oximes as a medical countermeasure both for protection against OPs poisoning and for postexposure treatment.