Cisatracurium besylate
[CAS# 96946-42-8]

Identification

• Classification: Biochemical >> Inhibitor >> Neuronal signaling >> Adrenergic receptor inhibitor
• Name: Cisatracurium besylate
• Synonyms: (1R,1'R,2R,2'R)-2,2'-[1,5-Pentanediylbis[oxy(3-oxo-3,1-propanediyl)]]bis[1-[(3,4-dimethoxyphenyl)methyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-isoquinolinium dibenzenesulfonate; Cisatracurium besilate
• Molecular Formula: C₅₃H₇₂N₂O₁₂^.2(C₆H₅O₃S);C₆₅H₈₂N₂O₁₈S₂
• Molecular Weight: 1243.48
• CAS Registry Number: 96946-42-8
• EC Number: 620-579-9
• SMILES: C[N@@+]1(CCC2=CC(=C(C=C2[C@H]1CC3=CC(=C(C=C3)OC)OC)OC)OC)CCC(=O)OCCCCCOC(=O)CC[N@+]4(CCC5=CC(=C(C=C5[C@H]4CC6=CC(=C(C=C6)OC)OC)OC)OC)C.C1=CC=C(C=C1)S(=O)(=O)[O-].C1=CC=C(C=C1)S(=O)(=O)[O-]

Properties

• Solubility: DMSO 250 mg/mL, Water 48 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H301-H319
• Precautionary Statements: P264-P264+P265-P270-P280-P301+P316-P305+P351+P338-P321-P330-P337+P317-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	4	H302
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	3	H311
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	1	H310
Acute toxicity	Acute Tox.	1	H330
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	1	H300

Discovory and Applicatios

Cisatracurium besylate is a neuromuscular blocking agent used in clinical practice during anesthesia to induce muscle relaxation. It is the besylate salt form of cisatracurium, which is a stereoisomer of atracurium. Cisatracurium is preferred over atracurium in certain clinical settings because of its more favorable pharmacological properties, including a lower incidence of histamine release and a reduced likelihood of causing cardiovascular side effects.

The primary use of cisatracurium besylate is to facilitate endotracheal intubation and provide muscle relaxation during general anesthesia for surgical procedures. It is particularly important in surgeries where muscle relaxation is required to improve surgical conditions, such as in orthopedic or abdominal surgeries. Additionally, cisatracurium is used in intensive care units (ICUs) for patients requiring mechanical ventilation, where muscle relaxation is necessary for optimal ventilation.

Cisatracurium works by binding to nicotinic receptors at the neuromuscular junction, preventing acetylcholine from binding and initiating muscle contraction. This leads to muscle paralysis. Unlike depolarizing agents such as succinylcholine, cisatracurium does not cause initial muscle contraction but rather works through competitive inhibition at the receptor. The drug has a relatively short onset and duration of action, which makes it ideal for use in controlled settings where rapid and reversible muscle relaxation is needed.

The pharmacokinetics of cisatracurium besylate are characterized by its non-renally dependent metabolism. Unlike many neuromuscular blockers that rely on renal function for clearance, cisatracurium is hydrolyzed by ester hydrolysis and Hofmann elimination. Hofmann elimination is a temperature- and pH-dependent process that occurs independently of liver or kidney function, making cisatracurium an appropriate choice for patients with impaired renal or hepatic function. This metabolic pathway allows for safer use in individuals with conditions such as renal failure, where other neuromuscular blockers might accumulate to dangerous levels.

Cisatracurium is typically administered intravenously and is dosed according to the patient’s body weight and clinical condition. The usual dose range for inducing muscle relaxation is approximately 0.1 to 0.2 mg/kg. The drug is often used in combination with other anesthetic agents to provide balanced anesthesia, ensuring both muscle relaxation and adequate sedation during surgery.

One of the significant advantages of cisatracurium besylate over other neuromuscular blockers is its reduced risk of histamine release. Histamine release can cause side effects such as hypotension, bronchospasm, and flushing, which are particularly problematic in patients with asthma or cardiovascular instability. Cisatracurium, by contrast, is less likely to induce these reactions, contributing to its safer profile in sensitive patient populations.

However, as with all neuromuscular blockers, the primary side effects of cisatracurium besylate relate to its ability to cause paralysis, which must be carefully monitored during administration. The drug does not provide analgesia or sedation, and patients must be appropriately anesthetized before administration. Monitoring of neuromuscular function is necessary to ensure that the drug is wearing off appropriately and to avoid residual paralysis. Reversal agents such as acetylcholinesterase inhibitors may be used to antagonize its effects and restore muscle function when necessary.

In conclusion, cisatracurium besylate is an important and widely used neuromuscular blocking agent in anesthesia, particularly due to its favorable safety profile and unique pharmacokinetic properties. It is especially beneficial for patients with compromised renal or hepatic function, as its metabolism is independent of these organs. The drug continues to be a critical component of anesthesia protocols in both surgical and intensive care settings.

References

1996. Pharmacodynamic Dose-Response and Safety Study of Cisatracurium (51W89) in Adult Surgical Patients During N2 O-O2-Opioid Anesthesia. Anesthesia and Analgesia, 83(4).
DOI: 10.1097/00000539-199610000-00030

2023. Cisatracurium Dosing Requirements in COVID-19 Compared to Non-COVID-19 Patients. Journal of Pharmacy Practice, 36(3).
DOI: 10.1177/08971900211052835

2024. Comparison of the Onset of Action, Maintenance, and Recovery of Three Weight-based Dosing of Cisatracurium in Patients with Morbid Obesity in Laparoscopic Bariatric Surgery: A Randomized Clinical Trial. Iranian Journal of Medical Sciences, 48(11).
DOI: 10.30476/ijms.2023.96131.2762