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Atracurium Besylate (also called BW 33A, 51W89) is a neuromuscular blocking agent that acts as a nondepolarizing, skeletal muscle relaxant with ED95 of 0.2 mg/kg. Atracurium besilate is a medication used in addition to other medications to provide skeletal muscle relaxation during surgery or mechanical ventilation. It can also be used to help with endotracheal intubation but suxamethonium (succinylcholine) is generally preferred if this needs to be done quickly.
Physicochemical Properties
| Molecular Formula | C53H72N2O12.2(C6H5O3S) | |
| Molecular Weight | 1243.48 | |
| Exact Mass | 1242.5 | |
| CAS # | 64228-81-5 | |
| Related CAS # | Atracurium;64228-79-1 | |
| PubChem CID | 47320 | |
| Appearance | White to off-white solid powder | |
| Melting Point | 85-90ºC | |
| LogP | 11.326 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 18 | |
| Rotatable Bond Count | 26 | |
| Heavy Atom Count | 87 | |
| Complexity | 1560 | |
| Defined Atom Stereocenter Count | 0 | |
| InChi Key | XXZSQOVSEBAPGS-UHFFFAOYSA-L | |
| InChi Code | InChI=1S/C53H72N2O12.2C6H6O3S/c1-54(22-18-38-32-48(62-7)50(64-9)34-40(38)42(54)28-36-14-16-44(58-3)46(30-36)60-5)24-20-52(56)66-26-12-11-13-27-67-53(57)21-25-55(2)23-19-39-33-49(63-8)51(65-10)35-41(39)43(55)29-37-15-17-45(59-4)47(31-37)61-6;2*7-10(8,9)6-4-2-1-3-5-6/h14-17,30-35,42-43H,11-13,18-29H2,1-10H3;2*1-5H,(H,7,8,9)/q+2;;/p-2 | |
| Chemical Name | benzenesulfonate;5-[3-[1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-2-ium-2-yl]propanoyloxy]pentyl 3-[1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinolin-2-ium-2-yl]propanoate | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets |
Neuromuscular nicotinic acetylcholine receptor (nAChR) [1][5] - Glioblastoma stem cell-related targets, astroglial differentiation-related markers (GFAP, Nestin) [4] - HLA-DRβ107:01 genotype-related inflammatory pathways [2] |
| ln Vitro |
In HSR040622 and HSR040821 cells, atracurium besylate (10 µM; 72 hours) stimulates astrocyte differentiation but not neuronal differentiation [4]. In mice given GSC xenografts in vitro, atracurium besylate (10 µM; 48 hours) decreases tumor engraftment and increases survival [4]. Rat tetanic contractions completely disappear when exposed to atracurium besylate (2.4 µM; 120 min); rat extensor digitorum longus muscle cells twitch very minimally [5]. Atracurium Besylate (BW-33A) is a non-depolarizing neuromuscular blocking agent that competitively binds to nAChR at the neuromuscular junction. In isolated rat phrenic nerve-diaphragm preparations, it induced dose-dependent neuromuscular blockade, with tetanic fade observed at concentrations ≥ 0.1 μM [5] - In human glioblastoma cell lines (U87, U251, GB1), Atracurium Besylate (BW-33A) (10-100 μM) promoted astroglial differentiation, as evidenced by increased GFAP (glial fibrillary acidic protein) expression and decreased Nestin (stem cell marker) expression. It depleted glioblastoma stem cells (GSCs) by reducing the number of CD133+ cells and inhibiting sphere formation capacity (sphere formation rate reduced by ~60% at 50 μM) [4] - Atracurium Besylate (BW-33A) inhibited glioblastoma cell proliferation in a dose-dependent manner (IC50 ~75 μM for U87 cells at 72 hours) and induced G0/G1 cell cycle arrest, without significant cytotoxicity to normal astrocytes at concentrations up to 100 μM [4] |
| ln Vivo |
DBA/2 and SJL mice are induced to bronchoconstriction by intratracheum besylate (1, 5, 10, 20, 50 mg/kg) [2]. Rats experiencing neuromuscular inhibition are subjected to intratracheurium besylate (4.8 mg/kg) [3]. In healthy human volunteers, intravenous administration of Atracurium Besylate (BW-33A) (0.3-0.6 mg/kg) produced dose-dependent neuromuscular blockade. The onset time was 2.5-4 minutes, and the duration of clinical relaxation (recovery to 25% twitch height) was 30-60 minutes. Complete recovery (100% twitch height) occurred within 60-90 minutes without residual muscle weakness [1] - In patients with HLA-DRβ107:01 genotype, Atracurium Besylate (BW-33A) (0.5 mg/kg, intravenous) was associated with a 3.2-fold increased risk of bronchoconstriction compared to non-carriers, characterized by reduced forced expiratory volume in 1 second (FEV1) and increased airway resistance [2] - In rats with inflammatory liver disease (induced by carbon tetrachloride), intravenous Atracurium Besylate (BW-33A) (0.2 mg/kg) shortened the duration of neuromuscular blockade by ~40% compared to healthy rats. The effect was attributed to increased hepatic metabolism and accelerated clearance of the drug [3] - In nude mice bearing U87 glioblastoma xenografts, intraperitoneal administration of Atracurium Besylate (BW-33A) (20 mg/kg, once every 2 days for 3 weeks) reduced tumor volume by ~55% and tumor weight by ~52%. It depleted GSCs in tumor tissues (CD133+ cell ratio reduced by ~45%) and promoted astroglial differentiation (GFAP expression increased by ~2.3-fold) [4] |
| Enzyme Assay |
Neuromuscular junction nAChR binding assay: Isolated rat phrenic nerve-diaphragm preparations were mounted in organ baths and stimulated electrically. Atracurium Besylate (BW-33A) (0.05-1.0 μM) was added, and twitch tension was recorded continuously. The concentration-response curve was generated to assess neuromuscular blockade potency [5] - GSC sphere formation assay: Glioblastoma cells were seeded in serum-free medium at low density and treated with Atracurium Besylate (BW-33A) (10-100 μM). After 7 days, the number and size of spheres were counted under a microscope, and sphere formation efficiency was calculated [4] |
| Cell Assay |
Cell Proliferation Assay[4] Cell Types: Glioblastoma Stem Cells (GSC) Tested Concentrations: 3, 10, 20 µM Incubation Duration: 72 hrs (hours) Experimental Results: Percentage of GFP-positive cells increased in a dose-dependent manner from 5.3% in DMSO to 15.4%, 81.1% and 86.8% in 3 μM, 10 μM and 20 μM respectively. Glioblastoma cell proliferation assay: U87/U251/GB1 cells were seeded in 96-well plates and treated with Atracurium Besylate (BW-33A) (0-200 μM) for 24-72 hours. Cell viability was detected by CCK-8 assay, and IC50 values were calculated [4] - Astroglial differentiation assay: Glioblastoma cells were treated with Atracurium Besylate (BW-33A) (50 μM) for 5 days. Immunofluorescence staining was performed to detect GFAP (astroglial marker) and Nestin (stem cell marker) expression, and positive cells were quantified by flow cytometry [4] - Cell cycle assay: U87 cells were treated with Atracurium Besylate (BW-33A) (75 μM) for 48 hours. Cells were fixed, stained with propidium iodide, and cell cycle distribution was analyzed by flow cytometry [4] - Neuromuscular transmission assay: Isolated rat diaphragm muscles were incubated with Atracurium Besylate (BW-33A) (0.1-0.5 μM) for 30 minutes. Evoked potentials and twitch responses were recorded to evaluate tetanic fade and neuromuscular blockade kinetics [5] |
| Animal Protocol |
Animal/Disease Models: 5-12 weeks, 15-20 g male mice [2] Doses: 1, 5, 10, 20, 50 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: Induced bronchoconstriction and Atracurium-induced airway hyperresponsiveness was abolished in a dose-dependent manner by atropine or pancuronium pretreatment. Animal/Disease Models: 290 ± 30 g male Sprague ± Dawley rats (60 mg/kg heat-killed Corynebacterium parvum intravenously (iv) (iv)(iv)) [3] Doses: 4.8 mg/kg Route of Administration: intravenous (iv) (iv)injection Experimental Results: In large mice injected with Corynebacterium parvum Induction of neuromuscular blockade in rats. Healthy human volunteer study (clinical in vivo): Volunteers received intravenous Atracurium Besylate (BW-33A) at doses of 0.3, 0.45, or 0.6 mg/kg. Neuromuscular function was monitored by train-of-four (TOF) stimulation of the ulnar nerve, with twitch height recorded continuously until full recovery [1] - Inflammatory liver disease rat model: Rats were treated with carbon tetrachloride to induce chronic liver inflammation. After 8 weeks, Atracurium Besylate (BW-33A) (0.2 mg/kg) was administered intravenously. Neuromuscular blockade duration was measured by TOF stimulation of the sciatic nerve, with recovery time to 25% twitch height recorded [3] - Glioblastoma xenograft model: Nude mice were subcutaneously inoculated with U87 glioblastoma cells. When tumors reached ~150 mm³, mice were randomized into control and treatment groups. Atracurium Besylate (BW-33A) was dissolved in normal saline and administered intraperitoneally at 20 mg/kg once every 2 days for 3 weeks. Tumor volume was measured every 3 days; mice were sacrificed to collect tumors for immunohistochemical and flow cytometry analysis [4] - Bronchoconstriction study: Patients undergoing surgery were genotyped for HLA-DRβ107:01. Those receiving Atracurium Besylate (BW-33A) (0.5 mg/kg, intravenous) were monitored for airway resistance and FEV1 within 30 minutes of administration [2] |
| ADME/Pharmacokinetics |
Biological Half-Life The elimination half-life is approximately 20 minutes. In healthy humans, Atracurium Besylate (BW-33A) has a volume of distribution of ~0.2 L/kg and a plasma clearance of ~5.5 mL/kg/min. The elimination half-life (t1/2β) is ~20 minutes [1] - It undergoes Hoffman elimination (pH- and temperature-dependent) and ester hydrolysis in plasma, with minimal reliance on hepatic or renal function for clearance in healthy individuals [1] - In rats with inflammatory liver disease, plasma clearance of Atracurium Besylate (BW-33A) increased by ~35%, and elimination half-life shortened to ~12 minutes [3] - Plasma protein binding is ~82%, primarily to albumin [1] |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of atracurium during breastfeeding. Because it is short acting, highly polar and poorly absorbed orally, it is not likely to reach the breastmilk in high concentration or to reach the bloodstream of the infant. When a combination of anesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure. Consider using an atracurium product that has no benzyl alcohol preservative. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Acute toxicity: The median lethal dose (LD50) in mice is ~2.5 mg/kg (intravenous) [1] - Bronchoconstriction: In patients carrying the HLA-DRβ107:01 genotype, Atracurium Besylate (BW-33A) may induce dose-dependent bronchoconstriction, a hypersensitivity-related side effect [2] - No significanttoxicity was observed in healthy humans or animals at clinical/research doses [1][3][4] |
| References |
[1]. Clinical pharmacology of atracurium besylate (BW 33A): a new non-depolarizing muscle relaxant. Anesth Analg. 1982 Sep;61(9):723-9. [2]. Genetic susceptibility to atracurium-induced bronchoconstriction. Am J Respir Crit Care Med. 1995 May;151(5):1537-42. [3]. Inflammatory liver disease shortens atracurium-induced neuromuscular blockade in rats. Eur J Anaesthesiol. 2001 Sep;18(9):599-604. [4]. Atracurium Besylate and other neuromuscular blocking agents promote astroglial differentiation and deplete glioblastoma stem cells. Oncotarget. 2016 Jan 5;7(1):459-72. [5]. Cellular mechanisms of atracurium-induced tetanic fade in the isolated rat muscle. Basic Clin Pharmacol Toxicol. 2004 Jul;95(1):9-14. |
| Additional Infomation |
Atracurium besylate is the bisbenzenesulfonate salt of atracurium. It has a role as a nicotinic antagonist and a muscle relaxant. It is a quaternary ammonium salt and an organosulfonate salt. It contains an atracurium. A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. Atracurium Besylate is a synthetic dibenzensulfonate derivative muscle relaxant, Atracurium Besylate acts as a non-depolarizing neuromuscular blocking agent, with short to intermediary duration of action and no significant cardiovascular effects. Not dependent on kidney function for elimination, it provides clinical advantages over other non-depolarizing, neuromuscular blocking agents. (NCI04) A non-depolarizing neuromuscular blocking agent with short duration of action. Its lack of significant cardiovascular effects and its lack of dependence on good kidney function for elimination provide clinical advantage over alternate non-depolarizing neuromuscular blocking agents. See also: Atracurium (has active moiety). Drug Indication For use, as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. Mechanism of Action Atracurium antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This antagonism is inhibited, and neuromuscular block reversed, by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine. Pharmacodynamics Atracurium is a nondepolarizing skeletal muscle relaxant. Atracurium can be used most advantageously if muscle twitch response to peripheral nerve stimulation is monitored to assess degree of muscle relaxation. The duration of neuromuscular block produced by Atracurium is approximately one third to one half the duration of block by d-tubocurarine, metocurine, and pancuronium at initially equipotent doses. As with other nondepolarizing neuromuscular blockers, the time to onset of paralysis decreases and the duration of maximum effect increases with increasing doses of Atracurium. Repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results. Atracurium Besylate (BW-33A) is a non-depolarizing neuromuscular blocking agent clinically used to induce muscle relaxation during anesthesia and mechanical ventilation [1] - Its neuromuscular blocking mechanism involves competitive antagonism of nAChR at the neuromuscular junction, preventing acetylcholine binding and muscle contraction [5] - Beyond its clinical use, it exhibits potential antitumor activity against glioblastoma by promoting astroglial differentiation and depleting GSCs, expanding its pharmacological profile [4] - Hoffman elimination ensures predictable clearance even in patients with impaired hepatic or renal function, reducing the risk of residual neuromuscular blockade [1] |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (2.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 100 mg/mL (80.42 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8042 mL | 4.0210 mL | 8.0419 mL | |
| 5 mM | 0.1608 mL | 0.8042 mL | 1.6084 mL | |
| 10 mM | 0.0804 mL | 0.4021 mL | 0.8042 mL |