Identification

Name
Cisatracurium
Accession Number
DB00565  (APRD00874)
Type
Small Molecule
Groups
Approved
Description

Cisatracurium is a nondepolarizing skeletal muscle relaxant for intravenous administration. Cisatracurium acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine. The neuromuscular block produced by cisatracurium besylate is readily antagonized by anticholinesterase agents once recovery has started. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at the time of reversal, the longer the time required for recovery of neuromuscular function. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action.

Structure
Thumb
Synonyms
  • Cisatracurium cation
Product Ingredients
IngredientUNIICASInChI Key
Cisatracurium besylate80YS8O1MBS96946-42-8XXZSQOVSEBAPGS-DONVQRBFSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cisatracurium Besylate InjectionSolution2 mgIntravenousMylan PharmaceuticalsNot applicableNot applicableCanada
Cisatracurium Besylate InjectionSolution2 mgIntravenousAccord Healthcare LimitedNot applicableNot applicableCanada
Cisatracurium Besylate InjectionSolution2 mgIntravenousPfizer2015-06-01Not applicableCanada
Cisatracurium Besylate Injection (preservative-free)Solution2 mgIntravenousMylan PharmaceuticalsNot applicableNot applicableCanada
Cisatracurium Besylate Injection Multi-doseSolution2 mgIntravenousFresenius KabiNot applicableNot applicableCanada
Cisatracurium Besylate Injection Single DoseSolution2 mgIntravenousFresenius KabiNot applicableNot applicableCanada
Cisatracurium Omega MultidoseSolution2 mgIntravenousOmega Laboratories Ltd2014-01-20Not applicableCanada
Cisatracurium Omega Single DoseSolution2 mgIntravenousOmega Laboratories Ltd2014-01-28Not applicableCanada
NimbexInjection2 mg/1mLIntravenousAbbVie Inc.2010-12-09Not applicableUs
NimbexInjection10 mg/1mLIntravenousAbbVie Inc.1995-12-15Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aj-cisatracuriumSolution2 mgIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Aj-cisatracuriumSolution2 mgIntravenousAgila Jamp Canada IncNot applicableNot applicableCanada
CisatracuriumInjection, solution10 mg/1mLIntravenousFresenius Kabi2015-02-26Not applicableUs
CisatracuriumInjection, solution2 mg/1mLIntravenousFresenius Kabi2015-02-26Not applicableUs
CisatracuriumInjection, solution2 mg/1mLIntravenousFresenius Kabi2015-02-26Not applicableUs
Cisatracurium BesylateInjection200 mg/20mLIntravenousTeva Parenteral Medicines, Inc.2018-09-04Not applicableUs
Cisatracurium BesylateInjection2 mg/1mLIntravenousSandoz2013-02-28Not applicableUs
Cisatracurium BesylateInjection10 mg/1mLIntravenousSandoz2012-07-16Not applicableUs
Cisatracurium BesylateInjection10 mg/1mLIntravenousJiangsu Hengrui Medicine Co., Ltd.2017-09-19Not applicableUs
Cisatracurium BesylateInjection2 mg/1mLIntravenousSandoz2013-02-28Not applicableUs
International/Other Brands
Nimbex Forte (GlaxoSmithKline) / Nimbium (GlaxoSmithKline)
Categories
UNII
QX62KLI41N
CAS number
96946-41-7
Weight
Average: 929.16
Monoisotopic: 928.507428607
Chemical Formula
C53H72N2O12
InChI Key
YXSLJKQTIDHPOT-LJCJQEJUSA-N
InChI
InChI=1S/C53H72N2O12/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/h14-17,30-35,42-43H,11-13,18-29H2,1-10H3/q+2/t42-,43-,54-,55-/m1/s1
IUPAC Name
(1R,2R)-1-[(3,4-dimethoxyphenyl)methyl]-2-(3-{[5-({3-[(1R,2R)-1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-2-ium-2-yl]propanoyl}oxy)pentyl]oxy}-3-oxopropyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-2-ium
SMILES
COC1=CC2=C(C=C1OC)[C@@H](CC1=CC(OC)=C(OC)C=C1)[N@@+](C)(CCC(=O)OCCCCCOC(=O)CC[N@@+]1(C)CCC3=C(C=C(OC)C(OC)=C3)[C@H]1CC1=CC(OC)=C(OC)C=C1)CC2

Pharmacology

Indication

For inpatients and outpatients as an adjunct to general anesthesia, to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgery or mechanical ventilation in the ICU.

Associated Therapies
Pharmacodynamics

Cisatracurium Besylate is a nondepolarizing skeletal muscle relaxant for intravenous administration. Cisatracurium Besylate acts on cholinergic receptors, blocking neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors such as neostigmine. The neuromuscular block produced by cisatracurium besylate is readily antagonized by anticholinesterase agents once recovery has started. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at the time of reversal, the longer the time required for recovery of neuromuscular function. Compared to other neuromuscular blocking agents, it is intermediate in its onset and duration of action.

Mechanism of action

Cisatracurium Besylate binds to the nicotinic acetycholine (cholinergic) receptors in the motor endplate and blocks access to the receptors. In the process of binding, the receptor is actually activated - causing a process known as depolarization. Since it is not degraded in the neuromuscular junction, the depolarized membrane remains depolarized and unresponsive to any other impulse, causing muscle paralysis.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

The binding of cisatracurium to plasma proteins has not been successfully studied due to its rapid degradation at physiologic pH.

Metabolism

The degradation of cisatracurium is largely independent of liver metabolism. Results from in vitro experiments suggest that cisatracurium undergoes Hofmann elimination (a pH and temperature-dependent chemical process) to form laudanosine and the monoquaternary acrylate metabolite. The monoquaternary acrylate undergoes hydrolysis by non-specific plasma esterases to form the monoquaternary alcohol metabolite. The monoquaternary alcohol metabolite can also undergo Hofmann elimination but at a much slower rate than cisatracurium. Laudanosine is further metabolized to desmethyl metabolites which are conjugated with glucuronic acid and excreted in the urine.

Route of elimination

Biliary and urinary excretion were the major routes of excretion of radioactivity (totaling >90% of the labeled dose within 7 hours of dosing), of which atracurium represented only a minor fraction.

Half life

Elimination half-life of 22 minutes.

Clearance
Not Available
Toxicity

Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Cisatracurium can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Cisatracurium is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Cisatracurium is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Cisatracurium is combined with Acetazolamide.
Food Interactions
Not Available

References

General References
  1. GlaxoSmithKline: NIMBEX injection product information [Link]
External Links
Human Metabolome Database
HMDB0240286
PubChem Compound
62886
PubChem Substance
46506666
ChemSpider
56615
ChEBI
140621
ChEMBL
CHEMBL1201248
Therapeutic Targets Database
DAP000196
PharmGKB
PA164744925
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Cisatracurium_besylate
ATC Codes
M03AC11 — Cisatracurium
AHFS Codes
  • 12:20.20 — Neuromuscular Blocking Agents
MSDS
Download (25.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedNot AvailableIntraocular Pressure1
3Active Not RecruitingTreatmentAcute Respiratory Distress Syndrome (ARDS)1
3CompletedPreventionFasciculations2
4CompletedNot AvailableNeuromuscular Block1
4CompletedPreventionNeuromuscular Blockade / Postoperative Complications1
4CompletedPreventionPostoperative Residual Curarization / Residual Neuromuscular Block1
4CompletedTreatmentAcute Respiratory Distress Syndrome (ARDS)1
4Enrolling by InvitationBasic ScienceARDS, Human / Critical Illness / Neuromuscular Blockade / Paralysis / Respiratory Distress Syndrome, Adult / Respiratory Failure1
4RecruitingTreatmentIntracranial Pressure Increase / Traumatic Brain Injury (TBI)1
4Unknown StatusTreatmentAcute Respiratory Distress Syndrome (ARDS)1
4Unknown StatusTreatmentAdrenal Suppression / Hemodynamics Instability1
4Unknown StatusTreatmentAnaesthesia therapy / Hemodynamics / Oxidative Stress1
4Unknown StatusTreatmentAnalgesia, Patient-Controlled / Arthroplasty / Gastric Resection1
4Unknown StatusTreatmentPerioperative/Postoperative Complications / PORC (Postoperative Residual Curarization)1
4WithdrawnNot AvailableNeuromuscular Blockade1
Not AvailableCompletedNot AvailableGender1
Not AvailableCompletedNot AvailableNeuromuscular Blockade2
Not AvailableCompletedTreatmentAnaesthesia therapy / Chronic Otitis Media1
Not AvailableCompletedTreatmentPostoperative pain1
Not AvailableNot Yet RecruitingTreatmentNeuromuscular Blockade1
Not AvailableRecruitingTreatmentNeuromuscular Blockade1
Not AvailableRecruitingTreatmentPostoperative Complications1
Not AvailableRecruitingTreatmentThe Comparison of the I-gel and Endotracheal Tube About in Different Ventilation Settings During Laparoscopic Surgery1
Not AvailableTerminatedTreatmentIntubations1
Not AvailableUnknown StatusNot AvailableC.Delivery; Surgery (Previous), Gynecological1
Not AvailableUnknown StatusNot AvailablePostcardiac Arrest Therapeutic Hypothermia1

Pharmacoeconomics

Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Baxter healthcare corp anesthesia critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Teva parenteral medicines inc
  • Abbott laboratories
Packagers
  • Abbott Laboratories Ltd.
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • GlaxoSmithKline Inc.
  • Hospira Inc.
  • Patheon Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous10 mg/1mL
Injection, solutionIntravenous2 mg/1mL
InjectionIntravenous10 mg/5mL
InjectionIntravenous10 mg/1mL
InjectionIntravenous2 mg/1mL
InjectionIntravenous20 mg/10mL
InjectionIntravenous200 mg/20mL
SolutionIntravenous2 mg
LiquidIntravenous2 mg
LiquidIntravenous10 mg
Prices
Unit descriptionCostUnit
Nimbex 10 mg/ml vial13.8USD ml
Nimbex 2 mg/ml vial2.91USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5453510No1995-09-262012-09-26Us
CA2087104No1998-08-182011-07-12Canada

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.32e-05 mg/mLALOGPS
logP3.41ALOGPS
logP-0.96ChemAxon
logS-7.6ALOGPS
pKa (Strongest Acidic)19.02ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area126.44 Å2ChemAxon
Rotatable Bond Count26ChemAxon
Refractivity280.68 m3·mol-1ChemAxon
Polarizability104.19 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9847
Blood Brain Barrier+0.9291
Caco-2 permeable-0.5966
P-glycoprotein substrateSubstrate0.6828
P-glycoprotein inhibitor IInhibitor0.7177
P-glycoprotein inhibitor IIInhibitor0.5808
Renal organic cation transporterNon-inhibitor0.5871
CYP450 2C9 substrateNon-substrate0.7994
CYP450 2D6 substrateNon-substrate0.7779
CYP450 3A4 substrateSubstrate0.6527
CYP450 1A2 substrateNon-inhibitor0.8244
CYP450 2C9 inhibitorNon-inhibitor0.7179
CYP450 2D6 inhibitorNon-inhibitor0.791
CYP450 2C19 inhibitorNon-inhibitor0.7048
CYP450 3A4 inhibitorNon-inhibitor0.7338
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8547
Ames testNon AMES toxic0.544
CarcinogenicityNon-carcinogens0.5302
BiodegradationReady biodegradable0.8169
Rat acute toxicity2.6124 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6043
hERG inhibition (predictor II)Inhibitor0.6507
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylisoquinolines. These are organic compounds containing an isoquinoline to which a benzyl group is attached.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoquinolines and derivatives
Sub Class
Benzylisoquinolines
Direct Parent
Benzylisoquinolines
Alternative Parents
Tetrahydroisoquinolines / Dimethoxybenzenes / Phenoxy compounds / Anisoles / Alkyl aryl ethers / Aralkylamines / Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Carboxylic acid esters / Azacyclic compounds
show 6 more
Substituents
Benzylisoquinoline / Tetrahydroisoquinoline / Dimethoxybenzene / O-dimethoxybenzene / Anisole / Phenol ether / Phenoxy compound / Methoxybenzene / Aralkylamine / Alkyl aryl ether
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Tuba Z, Maho S, Vizi ES: Synthesis and structure-activity relationships of neuromuscular blocking agents. Curr Med Chem. 2002 Aug;9(16):1507-36. [PubMed:12171561]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 10:03