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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
SynonymsNot Available
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nuromaxliquid1 mgintravenousAbbvie Corporation1992-12-312012-11-03Canada 5f16b84899037e23705f146ff57e3794121879cb055f0954756d94bc690476b4
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number106819-53-8
WeightAverage: 1106.14
Monoisotopic: 1104.4728398
Chemical FormulaC56H78Cl2N2O16
InChI KeyAPADFLLAXHIMFU-LGIHQUBZSA-L
InChI
InChI=1S/C56H78N2O16.2ClH/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;2*1H/q+2;;/p-2/t39-,40+,57-,58+;;
IUPAC Name
(1R,2S)-6,7,8-trimethoxy-2-methyl-2-{3-[(4-oxo-4-{3-[(1S,2R)-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 dichloride
SMILES
[Cl-].[Cl-].COC1=CC(C[C@@H]2C3=C(OC)C(OC)=C(OC)C=C3CC[N@@+]2(C)CCCOC(=O)CCC(=O)OCCC[N@@+]2(C)CCC3=C([C@@H]2CC2=CC(OC)=C(OC)C(OC)=C2)C(OC)=C(OC)C(OC)=C3)=CC(OC)=C1OC
Taxonomy
ClassificationNot classified
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
PropertyValueProbability
Human Intestinal Absorption-0.9919
Blood Brain Barrier+0.9419
Caco-2 permeable+0.6166
P-glycoprotein substrateSubstrate0.8274
P-glycoprotein inhibitor INon-inhibitor0.5903
P-glycoprotein inhibitor IIInhibitor0.6915
Renal organic cation transporterNon-inhibitor0.5328
CYP450 2C9 substrateNon-substrate0.8563
CYP450 2D6 substrateNon-substrate0.7468
CYP450 3A4 substrateSubstrate0.6802
CYP450 1A2 substrateNon-inhibitor0.9149
CYP450 2C9 inhibitorNon-inhibitor0.963
CYP450 2D6 inhibitorNon-inhibitor0.9124
CYP450 2C19 inhibitorNon-inhibitor0.9355
CYP450 3A4 inhibitorNon-inhibitor0.8601
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9305
Ames testNon AMES toxic0.6828
CarcinogenicityNon-carcinogens0.9133
BiodegradationNot ready biodegradable0.8219
Rat acute toxicity2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8508
hERG inhibition (predictor II)Non-inhibitor0.5553
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Liquidintravenous1 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility8.54e-05 mg/mLALOGPS
logP3.82ALOGPS
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
Polarizability113.31 Å3ChemAxon
Number of Rings6ChemAxon
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 References
  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
ATC CodesM03AC07
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
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 November 10, 2015 13:32