Identification

Name
Atracurium besylate
Accession Number
DB00732  (APRD00806)
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
  • Atracurium besilate
  • Atracurium besylate
  • Atracurium dibesylate
  • Besilate d'atracurium
  • Besilato de atracurio
External IDs
BW 33A / BW-33A / Wellcome 33-A-74
Active Moieties
NameKindUNIICASInChI Key
Atracuriumionic2GQ1IRY63P64228-79-1Not applicable
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Atracurium - (for Multiple Dose Vial - With Preservative)Solution10 mgIntravenousIvax Pharmaceuticals IncorporatedNot applicableNot applicableCanada
Atracurium - (for Single Dose )Solution10 mgIntravenousIvax Pharmaceuticals IncorporatedNot applicableNot applicableCanada
Atracurium Besylate InjectionSolution10 mgIntravenousHospira, Inc.1998-07-132012-08-03Canada
Atracurium Besylate InjectionLiquid10 mgIntravenousAbbott1998-02-112007-07-31Canada
Atracurium Besylate InjectionLiquid10 mgIntravenousSandoz Canada Incorporated1998-01-20Not applicableCanada
TracriumLiquid10 mgIntravenousAbbvie1990-12-312012-11-03Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Atracurium BesylateInjection, solution50 mg/5mLIntravenousHospira Worldwide, Inc.1997-03-282009-04-05Us
Atracurium BesylateInjection, solution10 mg/1mLIntravenousSagent Pharmaceuticals2012-05-01Not applicableUs
Atracurium BesylateInjection, solution100 mg/10mLIntravenousAurobindo Pharma2015-04-08Not applicableUs
Atracurium BesylateInjection, solution10 mg/1mLIntravenousHospira, Inc.2013-05-29Not applicableUs
Atracurium BesylateInjection, solution10 mg/1mLIntravenousBaxter Laboratories1997-02-172007-05-30Us
Atracurium BesylateInjection10 mg/1mLIntravenousBedford Pharmaceuticals1997-09-152013-03-31Us
Atracurium BesylateInjection, solution10 mg/1mLIntravenousMeitheal Pharmaceuticals Inc.2018-05-15Not applicableUs
Atracurium BesylateInjection, solution50 mg/5mLIntravenousAuro Medics Pharma Llc2015-04-08Not applicableUs
Atracurium BesylateInjection10 mg/1mLIntravenousBedford Pharmaceuticals2004-10-292013-03-31Us
Atracurium BesylateInjection, solution10 mg/1mLIntravenousMylan Institutional LLC2017-10-19Not applicableUs
Categories
UNII
40AX66P76P
CAS number
64228-81-5
Weight
Average: 1243.49
Monoisotopic: 1242.500406156
Chemical Formula
C65H82N2O18S2
InChI Key
XXZSQOVSEBAPGS-UHFFFAOYSA-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
IUPAC Name
1-[(3,4-dimethoxyphenyl)methyl]-2-[3-({5-[(3-{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=CC2=C(C=C1OC)C(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)C1CC1=CC(OC)=C(OC)C=C1)CC2

Pharmacology

Indication

For use, as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Associated Therapies
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.

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.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

The elimination half-life is approximately 20 minutes.

Clearance
Not Available
Toxicity

Excessive doses can be expected to produce enhanced pharmacological effects. Overdosage may increase the risk of histamine release and cardiovascular effects, especially hypotension.

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

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Atracurium besylate is combined with Acetophenazine.
Food Interactions
Not Available

References

Synthesis Reference

Steven A. Chamberlin, Ashok V. Bhatia, Deborah A. Davis, Keith A. Drengler, "Process for the preparation and isolation of atracurium besylate." U.S. Patent US5684154, issued September, 1995.

US5684154
General References
Not Available
External Links
KEGG Drug
D00758
PubChem Compound
47320
PubChem Substance
46504689
ChemSpider
43068
BindingDB
50149881
ChEBI
2915
ChEMBL
CHEMBL1200527
Therapeutic Targets Database
DAP000105
PharmGKB
PA164776840
RxList
RxList Drug Page
Wikipedia
Atracurium
AHFS Codes
  • 12:20.20 — Neuromuscular Blocking Agents
MSDS
Download (162 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedSupportive CareQuality of Ocular Akinesia (Onset and Duration)1
Not AvailableNot Yet RecruitingSupportive CareFemale Breast Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
Dosage forms
FormRouteStrength
InjectionIntravenous10 mg/1mL
Injection, solutionIntravenous10 mg/1mL
Injection, solutionIntravenous100 mg/10mL
Injection, solutionIntravenous50 mg/5mL
SolutionIntravenous10 mg
LiquidIntravenous10 mg
Prices
Unit descriptionCostUnit
Atracurium 10 mg/ml vial0.96USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)85-90Stenlake, J.B., Waigh, R.D., Dewar,G.H., Urwin, J. and Dhar, N.C.; U.S. Patent 4,179,507 December 18,1979; assigned to BurroughsWellcome Company.
water solubilityMiscibleNot 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
Polarizability104.67 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9907
Blood Brain Barrier+0.9367
Caco-2 permeable+0.6226
P-glycoprotein substrateSubstrate0.8276
P-glycoprotein inhibitor IInhibitor0.5282
P-glycoprotein inhibitor IIInhibitor0.6888
Renal organic cation transporterNon-inhibitor0.5447
CYP450 2C9 substrateNon-substrate0.8354
CYP450 2D6 substrateNon-substrate0.6895
CYP450 3A4 substrateSubstrate0.6913
CYP450 1A2 substrateNon-inhibitor0.9225
CYP450 2C9 inhibitorNon-inhibitor0.9468
CYP450 2D6 inhibitorNon-inhibitor0.8816
CYP450 2C19 inhibitorNon-inhibitor0.9107
CYP450 3A4 inhibitorNon-inhibitor0.8359
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9068
Ames testNon AMES toxic0.7032
CarcinogenicityNon-carcinogens0.9241
BiodegradationNot ready biodegradable0.7843
Rat acute toxicity2.5245 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8459
hERG inhibition (predictor II)Non-inhibitor0.5169
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
Benzenesulfonic acids and derivatives / Dimethoxybenzenes / Tetrahydroisoquinolines / 1-sulfo,2-unsubstituted aromatic compounds / Benzenesulfonyl compounds / Phenoxy compounds / Anisoles / Aralkylamines / Alkyl aryl ethers / Dicarboxylic acids and derivatives
show 11 more
Substituents
Benzylisoquinoline / Tetrahydroisoquinoline / Benzenesulfonate / O-dimethoxybenzene / Dimethoxybenzene / Arylsulfonic acid or derivatives / Benzenesulfonyl group / 1-sulfo,2-unsubstituted aromatic compound / Phenoxy compound / Anisole
show 30 more
Molecular Framework
Not Available
External Descriptors
quaternary ammonium salt, organosulfonate salt (CHEBI:2915)

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. Jonsson Fagerlund M, Dabrowski M, Eriksson LI: Pharmacological characteristics of the inhibition of nondepolarizing neuromuscular blocking agents at human adult muscle nicotinic acetylcholine receptor. Anesthesiology. 2009 Jun;110(6):1244-52. doi: 10.1097/ALN.0b013e31819fade3. [PubMed:19417616]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:42