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Identification
NameDoxacurium chloride
Accession NumberDB01135  (APRD00934, DB01334)
TypeSmall Molecule
GroupsApproved
Description

Doxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant for intravenous administration.

Structure
Thumb
Synonyms
SynonymLanguageCode
DoxacuriumNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
NuromaxNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number106819-53-8
WeightAverage: 1035.2223
Monoisotopic: 1034.535134458
Chemical FormulaC56H78N2O16
InChI KeyGBLRQXKSCRCLBZ-UHFFFAOYSA-N
InChI
InChI=1S/C56H78N2O16/c1-57(23-19-37-33-45(65-7)53(69-11)55(71-13)49(37)39(57)27-35-29-41(61-3)51(67-9)42(30-35)62-4)21-15-25-73-47(59)17-18-48(60)74-26-16-22-58(2)24-20-38-34-46(66-8)54(70-12)56(72-14)50(38)40(58)28-36-31-43(63-5)52(68-10)44(32-36)64-6/h29-34,39-40H,15-28H2,1-14H3/q+2
IUPAC Name
6,7,8-trimethoxy-2-methyl-2-(3-{[4-oxo-4-(3-{6,7,8-trimethoxy-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium-2-yl}propoxy)butanoyl]oxy}propyl)-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium
SMILES
COC1=CC(CC2C3=C(CC[N+]2(C)CCCOC(=O)CCC(=O)OCCC[N+]2(C)CCC4=C(C2CC2=CC(OC)=C(OC)C(OC)=C2)C(OC)=C(OC)C(OC)=C4)C=C(OC)C(OC)=C3OC)=CC(OC)=C1OC
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassIsoquinolines and Derivatives
SubclassBenzylisoquinolines
Direct parentBenzylisoquinolines
Alternative parentsStilbenes; Anisoles; Fatty Acid Esters; Alkyl Aryl Ethers; Dicarboxylic Acids and Derivatives; Carboxylic Acid Esters; Polyamines; Enolates
Substituentsstilbene; succinic_acid; anisole; phenol ether; alkyl aryl ether; fatty acid ester; dicarboxylic acid derivative; benzene; carboxylic acid ester; polyamine; enolate; ether; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the benzylisoquinolines. These are organic compounds containing an isoquinoline to which a benzyl group is attached.
Pharmacology
IndicationUsed to provide skeletal muscle relaxation as an adjunct to general anesthesia, for endotracheal intubation or to facilitate mechanical ventilation.
PharmacodynamicsDoxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant. The neuromuscular block produced by doxacurium chloride may be antagonized by anticholinesterase agents. As with other nondepolarizing neuromuscular blocking agents, the more profound the neuromuscular block at reversal, the longer the time and the greater the dose of anticholinesterase required for recovery of neuromuscular function. Doxacurium chloride is approximately 2.5 to 3 times more potent than pancuronium and 10 to 12 times more potent than metocurine.
Mechanism of actionDoxacurium chloride binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission (non-depolarizing). This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine.
AbsorptionNot Available
Volume of distribution
  • 0.11-0.43 L/kg [Healthy Young Adult Patients]
  • 0.17-0.55 L/kg [Kidney Transplant Patients]
  • 0.17-0.35 L/kg [Liver Transplant Patients]
Protein bindingApproximately 30%.
Metabolism

In vivo data from humans suggest that doxacurium chloride is not metabolized and that the major elimination pathway is excretion of unchanged drug in urine and bile.

Route of eliminationIn vivo data from humans suggest that NUROMAX is not metabolized and that the major elimination pathway is excretion of unchanged drug in urine and bile.
Half life99 minutes in normal healthy adults.
Clearance
  • 2.66 mL/min/kg [Healthy Young Adult Patients]
  • 1.23 mL/min/kg [Kidney Transplant Patients]
  • 2.3 mL/min/kg [Liver Transplant Patients]
  • 1.75 +/- 0.16 mL/min/kg [Elderly patients (70-83 yrs)]
  • 2.54 +/- 0.24 mL/min/kg [younger patients (19-39 yrs)]
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
Property Value Probability
Human Intestinal Absorption - 0.9919
Blood Brain Barrier + 0.9419
Caco-2 permeable + 0.6166
P-glycoprotein substrate Substrate 0.8274
P-glycoprotein inhibitor I Non-inhibitor 0.5903
P-glycoprotein inhibitor II Inhibitor 0.6915
Renal organic cation transporter Non-inhibitor 0.5328
CYP450 2C9 substrate Non-substrate 0.8563
CYP450 2D6 substrate Non-substrate 0.7468
CYP450 3A4 substrate Substrate 0.6802
CYP450 1A2 substrate Non-inhibitor 0.9149
CYP450 2C9 substrate Non-inhibitor 0.963
CYP450 2D6 substrate Non-inhibitor 0.9124
CYP450 2C19 substrate Non-inhibitor 0.9355
CYP450 3A4 substrate Non-inhibitor 0.8601
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9305
Ames test Non AMES toxic 0.6828
Carcinogenicity Non-carcinogens 0.9133
Biodegradation Not ready biodegradable 0.8219
Rat acute toxicity 2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8508
hERG inhibition (predictor II) Non-inhibitor 0.5553
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
PackagersNot Available
Dosage forms
FormRouteStrength
LiquidIntravenous
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility9.02e-05ALOGPS
logP3.44ALOGPS
logP-2.5ChemAxon
logS-7.1ALOGPS
pKa (Strongest Acidic)18.41ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area163.36 Å2ChemAxon
Rotatable Bond Count29ChemAxon
Refractivity302.15 m3·mol-1ChemAxon
Polarizability113.06 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Martinez EA, Wooldridge AA, Hartsfield SM, Mealey KL: Neuromuscular effects of doxacurium chloride in isoflurane-anesthetized dogs. Vet Surg. 1998 May-Jun;27(3):279-83. Pubmed
External Links
ResourceLink
KEGG DrugD00760
KEGG CompoundC07549
PubChem Compound60169
PubChem Substance46506733
ChemSpider54249
ChEBI4707
ChEMBLCHEMBL1237099
Therapeutic Targets DatabaseDAP000350
PharmGKBPA164744927
Drug Product Database1924656
RxListhttp://www.rxlist.com/cgi/generic3/doxacur.htm
WikipediaDoxacurium_chloride
ATC CodesM03AC07
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AmikacinThe agent increases the effect of muscle relaxant
AminophyllineTheophylline decreases the effect of muscle relaxant
AzathioprineThe agent decreases the effect of the muscle relaxant
CarbamazepineDecreases the effect of muscle relaxant
ClindamycinThe agent increases the effect of muscle relaxant
FosphenytoinPhenytoin decreases the effect of muscle relaxant
GentamicinThe agent increases the effect of muscle relaxant
LincomycinThe agent increases the effect of muscle relaxant
MercaptopurineThe agent dereases the effect of the muscle relaxant
NetilmicinThe agent increases the effect of muscle relaxant
OxtriphyllineTheophylline decreases the effect of muscle relaxant
PhenytoinPhenytoin decreases the effect of the muscle relaxant
PiperacillinThe agent increases the effect of the muscle relaxant
TheophyllineTheophylline decreases the effect of the muscle relaxant
TobramycinThe agent increases the effect of the muscle relaxant
Food InteractionsNot Available

Targets

1. Neuronal acetylcholine receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-2 Q15822 Details

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
  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
  3. Liu M, Dilger JP: Synergy between pairs of competitive antagonists at adult human muscle acetylcholine receptors. Anesth Analg. 2008 Aug;107(2):525-33. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Muscarinic acetylcholine receptor M2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Muscarinic acetylcholine receptor M2 P08172 Details

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
  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
  3. Hou VY, Hirshman CA, Emala CW: Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. Anesthesiology. 1998 Mar;88(3):744-50. Pubmed

Enzymes

1. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Basta SJ, Savarese JJ, Ali HH, Embree PB, Schwartz AF, Rudd GD, Wastila WB: Clinical pharmacology of doxacurium chloride. A new long-acting nondepolarizing muscle relaxant. Anesthesiology. 1988 Oct;69(4):478-86. Pubmed
  2. Dresner DL, Basta SJ, Ali HH, Schwartz AF, Embree PB, Wargin WA, Lai AA, Brady KA, Savarese JJ: Pharmacokinetics and pharmacodynamics of doxacurium in young and elderly patients during isoflurane anesthesia. Anesth Analg. 1990 Nov;71(5):498-502. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13