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Identification
NameDoxacurium chloride
Accession NumberDB01135  (APRD00934, DB01334)
TypeSmall Molecule
GroupsApproved
DescriptionDoxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant for intravenous administration.
Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nuromaxliquid1 mgintravenousAbbvie Corporation1992-12-312012-11-03Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIMN728NK085
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.
Related Articles
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:9605239 ]
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

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
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. Liu M, Dilger JP: Synergy between pairs of competitive antagonists at adult human muscle acetylcholine receptors. Anesth Analg. 2008 Aug;107(2):525-33. doi: 10.1213/ane.0b013e31817b4469. [PubMed:18633030 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then trigge...
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 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. Hou VY, Hirshman CA, Emala CW: Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. Anesthesiology. 1998 Mar;88(3):744-50. [PubMed:9523819 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
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:2972233 ]
  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:2145783 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23