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Identification
Name Doxacurium chloride
Accession Number DB01135 (APRD00934, DB01334)
Type small molecule
Groups approved
Description

Doxacurium chloride is a long-acting, nondepolarizing skeletal muscle relaxant for intravenous administration.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Nuromax
Brand mixtures Not Available
Categories
  • Neuromuscular Nondepolarizing Agents
CAS number 106819-53-8
Weight Average: 1035.2223
Monoisotopic: 1034.535134458
Chemical Formula C56H78N2O16
InChI Key InChIKey=GBLRQXKSCRCLBZ-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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzylisoquinolines
Substructures
  • Carboxylic Acids and Derivatives
  • Anions
  • Acetates
  • Phenols and Derivatives
  • Benzylisoquinolines
  • Ethers
  • Benzene and Derivatives
  • Quaternary Ammonium Salts
  • Catechols
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • (Iso)quinolines and Derivatives
  • Keto-Acids
  • Phenyl Esters
  • Amphetamines
  • Catecholamines and Derivatives
  • Cations
Pharmacology
Indication Used to provide skeletal muscle relaxation as an adjunct to general anesthesia, for endotracheal intubation or to facilitate mechanical ventilation.
Pharmacodynamics Doxacurium 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 action Doxacurium 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.
Absorption Not 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 binding Approximately 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 elimination In 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 life 99 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)]
Toxicity Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Abbott laboratories
Packagers Not Available
Dosage forms
Form Route Strength
Liquid Intravenous
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 9.02e-05 g/l ALOGPS
logP 3.44 ALOGPS
logP -2.5 ChemAxon
logS -7.1 ALOGPS
pKa (strongest acidic) 18.41 ChemAxon
pKa (strongest basic) -4.1 ChemAxon
physiological charge 2 ChemAxon
hydrogen acceptor count 14 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 163.36 ChemAxon
rotatable bond count 29 ChemAxon
refractivity 302.15 ChemAxon
polarizability 113.06 ChemAxon
References
Synthesis Reference Not 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
Resource Link
KEGG Drug D00760 Link_out
KEGG Compound C07549 Link_out
PubChem Compound 60169 Link_out
PubChem Substance 46506733 Link_out
ChemSpider 54249 Link_out
ChEBI 4707 Link_out
ChEMBL 4707 Link_out
Therapeutic Targets Database DAP000350 Link_out
PharmGKB PA164744927 Link_out
Drug Product Database 1924656 Link_out
RxList http://www.rxlist.com/cgi/generic3/doxacur.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Doxacurium_chloride Link_out
ATC Codes
  • M03AC07
AHFS Codes
  • 12:20.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amikacin The agent increases the effect of muscle relaxant
Aminophylline Theophylline decreases the effect of muscle relaxant
Azathioprine The agent decreases the effect of the muscle relaxant
Carbamazepine Decreases the effect of muscle relaxant
Clindamycin The agent increases the effect of muscle relaxant
Fosphenytoin Phenytoin decreases the effect of muscle relaxant
Gentamicin The agent increases the effect of muscle relaxant
Lincomycin The agent increases the effect of muscle relaxant
Mercaptopurine The agent dereases the effect of the muscle relaxant
Netilmicin The agent increases the effect of muscle relaxant
Oxtriphylline Theophylline decreases the effect of muscle relaxant
Phenytoin Phenytoin decreases the effect of the muscle relaxant
Piperacillin The agent increases the effect of the muscle relaxant
Theophylline Theophylline decreases the effect of the muscle relaxant
Tobramycin The agent increases the effect of the muscle relaxant
Food Interactions Not Available
Targets

1. Neuronal acetylcholine receptor subunit alpha-2

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: Q15822 Link_out
Gene: CHRNA2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: antagonist

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

Organism class: human
UniProt ID: P08172 Link_out
Gene: CHRM2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: substrate

An acylcholine + H(2)O = choline + a carboxylate

UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19