You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameCisatracurium besylate
Accession NumberDB00565  (APRD00874)
TypeSmall Molecule
GroupsApproved
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
(1R-cis,1'R-cis)-2,2'-{pentane-1,5-diylbis[oxy(3-oxopropane-3,1-diyl)]}bis[1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolinium] bisbenzenesulfonate
(1R-cis,1'R-cis)-atracurium besylate
(1R,1'R,2R,2'r)-atracurium besylate
Besilate de cisatracurium
Besilato de cisatracurio
Cisatracurii besilas
Cisatracurium besilate
Cisatracurium dibenzenesulfonate
Cisatracurium-Kation
External Identifiers
  • 51W89
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aj-cisatracuriumsolution2 mgintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Aj-cisatracuriumsolution2 mgintravenousAgila Jamp Canada IncNot applicableNot applicableCanada
Cisatracurium Besylate Injectionsolution2 mgintravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Cisatracurium Besylate Injectionsolution2 mgintravenousHospira Healthcare Corporation2015-06-01Not applicableCanada
Cisatracurium Besylate Injection (preservative-free)solution2 mgintravenousMylan Pharmaceuticals UlcNot applicableNot applicableCanada
Cisatracurium Besylate Injection Multi-dosesolution2 mgintravenousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Cisatracurium Besylate Injection Single Dosesolution2 mgintravenousFresenius Kabi Canada LtdNot applicableNot applicableCanada
Cisatracurium Omega Multidosesolution2 mgintravenousOmega Laboratories Ltd2014-01-20Not applicableCanada
Cisatracurium Omega Single Dosesolution2 mgintravenousOmega Laboratories Ltd2014-01-28Not applicableCanada
Nimbexinjection2 mg/mLintravenousAbb Vie Inc.2010-12-09Not applicableUs
Nimbexliquid2 mgintravenousAbbvie Corporation1997-04-07Not applicableCanada
Nimbexinjection10 mg/mLintravenousAbb Vie Inc.1995-12-15Not applicableUs
Nimbexinjection2 mg/mLintravenousAbb Vie Inc.2010-12-09Not applicableUs
Nimbex 10mg/mlliquid10 mgintravenousAbbott Laboratories, Limited1997-03-172008-06-06Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Cisatracuriuminjection, solution10 mg/mLintravenousFresenius Kabi USA, LLC2015-02-26Not applicableUs
Cisatracuriuminjection, solution2 mg/mLintravenousFresenius Kabi USA, LLC2015-02-26Not applicableUs
Cisatracuriuminjection, solution2 mg/mLintravenousFresenius Kabi USA, LLC2015-02-26Not applicableUs
Cisatracurium Besylateinjection, solution2 mg/mLintravenousSagent Pharmaceuticals2012-09-27Not applicableUs
Cisatracurium Besylateinjection2 mg/mLintravenousSandoz Inc2012-07-16Not applicableUs
Cisatracurium Besylateinjection, solution10 mg/mLintravenousSagent Pharmaceuticals2012-09-27Not applicableUs
Cisatracurium Besylateinjection, solution2 mg/mLintravenousSagent Pharmaceuticals2012-09-27Not applicableUs
Cisatracurium Besylateinjection10 mg/mLintravenousSandoz Inc2013-02-28Not applicableUs
Cisatracurium Besylateinjection2 mg/mLintravenousSandoz Inc2013-02-28Not applicableUs
Cisatracurium Besylateinjection2 mg/mLintravenousSandoz Inc2013-02-28Not applicableUs
Cisatracurium Besylateinjection10 mg/mLintravenousSandoz Inc2012-07-16Not applicableUs
Cisatracurium Besylateinjection2 mg/mLintravenousSandoz Inc2012-07-16Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Nimbex ForteGlaxoSmithKline
NimbiumGlaxoSmithKline
Brand mixturesNot Available
SaltsNot Available
Categories
UNII80YS8O1MBS
CAS number96946-42-8
WeightAverage: 1243.479
Monoisotopic: 1242.50040521
Chemical FormulaC65H82N2O18S2
InChI KeyInChIKey=XXZSQOVSEBAPGS-DONVQRBFSA-L
InChI
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/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 dibenzenesulfonate
SMILES
[O-]S(=O)(=O)C1=CC=CC=C1.[O-]S(=O)(=O)C1=CC=CC=C1.COC1=C(OC)C=C(C[C@@H]2C3=CC(OC)=C(OC)C=C3CC[N@+]2(C)CCC(=O)OCCCCCOC(=O)CC[N@@+]2(C)CCC3=CC(OC)=C(OC)C=C3[[email protected]]2CC2=CC(OC)=C(OC)C=C2)C=C1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub ClassBenzylisoquinolines
Direct ParentBenzylisoquinolines
Alternative Parents
Substituents
  • Benzylisoquinoline
  • O-dimethoxybenzene
  • Dimethoxybenzene
  • Benzenesulfonate
  • Tetrahydroisoquinoline
  • 1-sulfo,2-unsubstituted aromatic compound
  • Arylsulfonic acid or derivatives
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aralkylamine
  • Alkyl aryl ether
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonic acid
  • Quaternary ammonium salt
  • Carboxylic acid ester
  • Azacycle
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic cation
  • Aromatic homomonocyclic compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkNot Available
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsCisatracurium 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 actionCisatracurium 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingThe 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.

SubstrateEnzymesProduct
Cisatracurium besylate
Not Available
laudanosineDetails
Cisatracurium besylate
Not Available
Monoquaternary acrylateDetails
Route of eliminationBiliary 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 lifeElimination half-life of 22 minutes.
ClearanceNot Available
ToxicityOverdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
Dosage forms
FormRouteStrength
Injection, solutionintravenous10 mg/mL
Injection, solutionintravenous2 mg/mL
Solutionintravenous2 mg
Injectionintravenous10 mg/mL
Injectionintravenous2 mg/mL
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)
CA2087104 No1998-08-182011-07-12Canada
US5453510 No1992-09-262012-09-26Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility4.17e-05 mg/mLALOGPS
logP3.34ALOGPS
logP-0.96ChemAxon
logS-7.5ALOGPS
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 Count28ChemAxon
Refractivity280.68 m3·mol-1ChemAxon
Polarizability105.55 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (25.2 KB)
Interactions
Drug Interactions
Drug
AmikacinAmikacin may increase the activities of Cisatracurium besylate.
AmlodipineAmlodipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
AmrinoneAmrinone may increase the neuromuscular blocking activities of Cisatracurium besylate.
ArbekacinArbekacin may increase the activities of Cisatracurium besylate.
BepridilBepridil may increase the neuromuscular blocking activities of Cisatracurium besylate.
Botulinum Toxin Type ABotulinum Toxin Type A may increase the neuromuscular blocking activities of Cisatracurium besylate.
Botulinum Toxin Type BCisatracurium besylate may increase the neuromuscular blocking activities of Botulinum Toxin Type B.
CapreomycinCapreomycin may increase the neuromuscular blocking activities of Cisatracurium besylate.
ClindamycinClindamycin may increase the neuromuscular blocking activities of Cisatracurium besylate.
ColistimethateColistimethate may increase the neuromuscular blocking activities of Cisatracurium besylate.
CyclosporineCyclosporine may increase the neuromuscular blocking activities of Cisatracurium besylate.
DigoxinCisatracurium besylate may increase the arrhythmogenic activities of Digoxin.
FelodipineFelodipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
FludrocortisoneCisatracurium besylate may increase the adverse neuromuscular activities of Fludrocortisone.
FlunarizineFlunarizine may increase the neuromuscular blocking activities of Cisatracurium besylate.
FramycetinFramycetin may increase the activities of Cisatracurium besylate.
GabapentinGabapentin may increase the neuromuscular blocking activities of Cisatracurium besylate.
GentamicinGentamicin may increase the activities of Cisatracurium besylate.
IsofluraneIsoflurane may increase the neuromuscular blocking activities of Cisatracurium besylate.
IsradipineIsradipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
KanamycinKanamycin may increase the activities of Cisatracurium besylate.
KetorolacThe risk or severity of adverse effects can be increased when Ketorolac is combined with Cisatracurium besylate.
LamotrigineLamotrigine may increase the neuromuscular blocking activities of Cisatracurium besylate.
LercanidipineLercanidipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
LincomycinLincomycin may increase the neuromuscular blocking activities of Cisatracurium besylate.
LithiumLithium may increase the neuromuscular blocking activities of Cisatracurium besylate.
Magnesium SulfateMagnesium Sulfate may increase the neuromuscular blocking activities of Cisatracurium besylate.
MinocyclineMinocycline may increase the neuromuscular blocking activities of Cisatracurium besylate.
NeomycinNeomycin may increase the activities of Cisatracurium besylate.
NetilmicinNetilmicin may increase the activities of Cisatracurium besylate.
NicardipineNicardipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
NimodipineNimodipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
NisoldipineNisoldipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
NitrendipineNitrendipine may increase the neuromuscular blocking activities of Cisatracurium besylate.
OxytetracyclineOxytetracycline may increase the neuromuscular blocking activities of Cisatracurium besylate.
PerhexilinePerhexiline may increase the neuromuscular blocking activities of Cisatracurium besylate.
PhenytoinPhenytoin may decrease the neuromuscular blocking activities of Cisatracurium besylate.
Polymyxin B SulfatePolymyxin B Sulfate may increase the neuromuscular blocking activities of Cisatracurium besylate.
PrenylaminePrenylamine may increase the neuromuscular blocking activities of Cisatracurium besylate.
ProcainamideProcainamide may increase the neuromuscular blocking activities of Cisatracurium besylate.
QuinidineQuinidine may increase the neuromuscular blocking activities of Cisatracurium besylate.
QuinineQuinine may increase the neuromuscular blocking activities of Cisatracurium besylate.
RibostamycinRibostamycin may increase the activities of Cisatracurium besylate.
RisedronateRisedronate may increase the neuromuscular blocking activities of Cisatracurium besylate.
SpectinomycinSpectinomycin may increase the activities of Cisatracurium besylate.
SpironolactoneSpironolactone may increase the neuromuscular blocking activities of Cisatracurium besylate.
StreptomycinStreptomycin may increase the activities of Cisatracurium besylate.
TacrineTacrine may decrease the neuromuscular blocking activities of Cisatracurium besylate.
TobramycinTobramycin may increase the activities of Cisatracurium besylate.
TorasemideTorasemide may decrease the neuromuscular blocking activities of Cisatracurium besylate.
VancomycinVancomycin may increase the neuromuscular blocking activities of Cisatracurium besylate.
VerapamilVerapamil may increase the neuromuscular blocking activities of Cisatracurium besylate.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
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
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 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 22, 2015 14:39