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]

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].

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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]

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].

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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]

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 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.

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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/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.

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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.

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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]

Biological half-life
Elimination half-life is approximately 20 minutes.

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In healthy human bodies, the volume of distribution of atracurium besylate (BW-33A) is approximately 0.2 L/kg, and the plasma clearance rate is approximately 5.5 mL/kg/min. Elimination half-life (t1/2β) is approximately 20 minutes [1]
-In healthy individuals, atracurium besylate (BW-33A) is mainly cleared from plasma by Hoffmann elimination (pH and temperature dependent) and ester hydrolysis, with very low dependence on hepatic and renal function [1]
-In rats with inflammatory liver disease, the plasma clearance rate of atracurium besylate (BW-33A) is increased by approximately 35%, and the elimination half-life is shortened to approximately 12 minutes [3]
-Plasma protein binding is approximately 82%, mainly bound to albumin [1]

Effects During Pregnancy and Lactation
◉ Summary of Use During Lactation
There is currently no information regarding the use of atracurium during lactation. Due to its short duration of action, high polarity, and poor oral absorption, it is unlikely to enter breast milk or the infant's bloodstream at high concentrations. When multiple anesthetics are used during surgery, follow the medication recommendations for the drug most likely to cause adverse reactions during the procedure. Consider using atracurium products without benzyl alcohol preservative.
◉ Effects on Breastfed Infants
As of the revision date, no relevant published information was found.
◉ Effects on Lactation and Breast Milk
As of the revision date, no relevant published information was found.

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Acute toxicity: The median lethal dose (LD50) in mice is approximately 2.5 mg/kg (intravenous injection) [1]
- Bronchoconstriction: In patients carrying the HLA-DRβ107:01 genotype, atracurium besylate (BW-33A) may induce dose-dependent bronchoconstriction, a side effect associated with hypersensitivity [2]
- No significant toxicity was observed in healthy humans and animals at clinical/investigation doses [1][3][4]

[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.

Atracurium besylate is the dibenzenesulfonate of atracurium. It is a nicotinic receptor antagonist and muscle relaxant. It is a quaternary ammonium salt and an organic sulfonate. It contains atracurium. It is a short-duration, non-depolarizing neuromuscular blockade. It has clinical advantages over other non-depolarizing neuromuscular blockades due to its lack of significant cardiovascular side effects and its clearance without dependence on good renal function. Atracurium besylate is a synthetic dibenzenesulfonate derivative muscle relaxant. Atracurium besylate is a non-depolarizing neuromuscular blockade with a short to moderate duration of action and no significant cardiovascular side effects. It has clinical advantages over other non-depolarizing neuromuscular blockades due to its clearance without dependence on renal function. (NCI04) It is a short-duration, non-depolarizing neuromuscular blockade. It has clinical advantages over other non-depolarizing neuromuscular blockades due to its lack of significant cardiovascular side effects and its clearance without dependence on good renal function. See also: Atracurium (containing the active ingredient). Drug Indications For adjunctive 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 competitively binding to cholinergic receptors on the motor endplate. This antagonism can be inhibited by acetylcholinesterase inhibitors such as neostigmine, ethanochloride, and pyridostigmine, thereby reversing neuromuscular blockade. Pharmacodynamics Atracurium is a non-depolarizing skeletal muscle relaxant. Its use is most advantageous when monitoring muscle twitching responses to peripheral nerve stimulation to assess the degree of muscle relaxation. The duration of neuromuscular blockade produced by atracurium is approximately one-third to one-half that of d-tubocurarine, metocurin, and pancuronium bromide at their initial equivalent doses. As with other non-depolarizing neuromuscular blocking agents, atracurium's onset time decreases and its duration of maximal effect increases with increasing dose. Repeated administration of atracurium maintenance doses does not have a cumulative effect on the duration of neuromuscular blockade if the patient is allowed to begin recovery before repeat dosing. Furthermore, the time required for recovery after repeat dosing does not change with increasing additional doses. Therefore, repeat dosing can be performed relatively regularly with predictable results.

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Atracurium besylate (BW-33A) is a non-depolarizing neuromuscular blockade agent used clinically to induce muscle relaxation during anesthesia and mechanical ventilation[1]
- Its neuromuscular blocking mechanism involves competitive antagonism of nAChR at the neuromuscular junction, thereby preventing acetylcholine binding and muscle contraction[5]
- In addition to its clinical applications, it also has potential anti-glioblastoma activity, which can be extended by promoting astrocyte differentiation and depleting glioblastoma stem cells (GSCs)[4]
- The Hoffmann elimination pathway ensures predictable clearance even in patients with impaired hepatic and renal function, thereby reducing the risk of residual neuromuscular blockade[1]

C53H72N2O12.2(C6H5O3S)

1243.48

1242.5

64228-81-5

Atracurium;64228-79-1

47320

White to off-white solid powder

85-90ºC

11.326

0

18

26

87

1560

0

XXZSQOVSEBAPGS-UHFFFAOYSA-L

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

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

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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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.

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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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)