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Identification
NameMivacurium
Accession NumberDB01226  (APRD01119)
TypeSmall Molecule
GroupsApproved
Description

Mivacurium is a bisbenzylisoquinolinium based neuromuscular blocker or muscle relaxant. It binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission.

Structure
Thumb
Synonyms
Mivacurium
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mivacronsolution2 mg/mLintravenousAbb Vie Inc.2015-01-30Not applicableUs
Mivacronliquid2 mgintravenousAbbvie Corporation1994-12-312012-11-03Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Mivacurium chloride
106861-44-3
Thumb
  • InChI Key: WMSYWJSZGVOIJW-ONUALHDOSA-L
  • Monoisotopic Mass: 1098.4986607
  • Average Mass: 1100.18
DBSALT001359
Categories
UNII77D66S9Q93
CAS number133814-19-4
WeightAverage: 1029.2608
Monoisotopic: 1028.560955278
Chemical FormulaC58H80N2O14
InChI KeyInChIKey=ILVYCEVXHALBSC-OTBYEXOQSA-N
InChI
InChI=1S/C58H80N2O14/c1-59(25-21-41-35-47(63-3)49(65-5)37-43(41)45(59)29-39-31-51(67-7)57(71-11)52(32-39)68-8)23-17-27-73-55(61)19-15-13-14-16-20-56(62)74-28-18-24-60(2)26-22-42-36-48(64-4)50(66-6)38-44(42)46(60)30-40-33-53(69-9)58(72-12)54(34-40)70-10/h13-14,31-38,45-46H,15-30H2,1-12H3/q+2/b14-13+/t45-,46-,59?,60?/m1/s1
IUPAC Name
(1R)-2-(3-{[(4E)-8-{3-[(1R)-6,7-dimethoxy-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium-2-yl]propoxy}-8-oxooct-4-enoyl]oxy}propyl)-6,7-dimethoxy-2-methyl-1-[(3,4,5-trimethoxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinolin-2-ium
SMILES
COC1=CC(C[C@@H]2C3=CC(OC)=C(OC)C=C3CC[N+]2(C)CCCOC(=O)CC\C=C\CCC(=O)OCCC[N+]2(C)CCC3=CC(OC)=C(OC)C=C3[[email protected]]2CC2=CC(OC)=C(OC)C(OC)=C2)=CC(OC)=C1OC
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoquinolines and derivatives
Sub ClassBenzylisoquinolines
Direct ParentBenzylisoquinolines
Alternative Parents
Substituents
  • Benzylisoquinoline
  • Tetrahydroisoquinoline
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aralkylamine
  • Fatty acid ester
  • Alkyl aryl ether
  • Fatty acyl
  • Benzenoid
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Quaternary ammonium salt
  • Carboxylic acid ester
  • Azacycle
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic cation
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor inpatients and outpatients, as an adjunct to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.
PharmacodynamicsMivacurium is a short-acting, nondepolarizing skeletal neuromuscular blocking agent which is hydrolyzed by plasma cholinesterase. Mivacurium results in a blockade of neuromuscular transmission by binding competitively with cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine. The neuromuscular block produced by mivacurium is readily antagonized by anticholinesterase agents. The deeper the level of neuromuscular block at reversal, the longer the time required for recovery of neuromuscular function and the greater the dose of anticholinesterase agent required. Because spontaneous recovery after mivacurium is rapid, routine reversal may not always result in a clinical benefit.
Mechanism of actionMivacurium binds competitively to cholinergic receptors on the motor end-plate to antagonize the action of acetylcholine, resulting in a block of neuromuscular transmission. This action is antagonized by acetylcholinesterase inhibitors, such as neostigmine.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingThe protein binding of mivacurium has not been determined due to its rapid hydrolysis by plasma cholinesterase.
Metabolism

Extensive and rapid via enzymatic hydrolysis catalyzed by plasma cholinesterase. Biotransformation may be significantly slowed in patients with abnormal or decreased plasma cholinesterase activity, especially individuals with a homozygous atypical cholinesterase gene abnormality.

Route of eliminationNot Available
Half lifeThe mean elimination half-life ranges from 1.7 to 2.6 minutes in healthy, young adults administered 0.1 to 0.25 mg/kg mivacurium. In 9 patients with end-stage liver disease undergoing liver transplant surgery, plasma clearance was approximately 50% lower than that in 8 control patients with normal hepatic function, while the elimination half-life increased to 4.4 minutes from the 1.8 minute control value.
ClearanceNot Available
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-0.9832
Blood Brain Barrier+0.9465
Caco-2 permeable+0.629
P-glycoprotein substrateSubstrate0.8476
P-glycoprotein inhibitor INon-inhibitor0.5119
P-glycoprotein inhibitor IIInhibitor0.7645
Renal organic cation transporterNon-inhibitor0.5515
CYP450 2C9 substrateNon-substrate0.8376
CYP450 2D6 substrateNon-substrate0.7529
CYP450 3A4 substrateSubstrate0.6975
CYP450 1A2 substrateNon-inhibitor0.8986
CYP450 2C9 inhibitorNon-inhibitor0.9583
CYP450 2D6 inhibitorNon-inhibitor0.8914
CYP450 2C19 inhibitorNon-inhibitor0.9348
CYP450 3A4 inhibitorNon-inhibitor0.8426
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.919
Ames testNon AMES toxic0.7046
CarcinogenicityNon-carcinogens0.9137
BiodegradationNot ready biodegradable0.876
Rat acute toxicity2.6607 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8134
hERG inhibition (predictor II)Non-inhibitor0.6401
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Liquidintravenous2 mg
Solutionintravenous2 mg/mL
PricesNot Available
PatentsNot Available
Properties
StateLiquid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility3.26e-05 mg/mLALOGPS
logP3.8ALOGPS
logP-0.76ChemAxon
logS-7.5ALOGPS
pKa (Strongest Acidic)18.59ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area144.9 Å2ChemAxon
Rotatable Bond Count30ChemAxon
Refractivity308.74 m3·mol-1ChemAxon
Polarizability116.68 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 Reference

Maurizio Francesco Velati, Andrea Busca, Cristina Manfrotto, Marco Nicolini, Claudio Gianluca Pozzoli, “Process for the preparation of mivacurium chloride.” U.S. Patent US20070293534, issued December 20, 2007.

US20070293534
General ReferencesNot Available
External Links
ATC CodesM03AC10
AHFS Codes
  • 12:20.00
PDB EntriesNot Available
FDA labelDownload (1.5 MB)
MSDSDownload (25.3 KB)
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. Ihmsen H, Schmidt J, Schwilden H, Schmitt HJ, Muenster T: Influence of disease progression on the neuromuscular blocking effect of mivacurium in children and adolescents with Duchenne muscular dystrophy. Anesthesiology. 2009 May;110(5):1016-9. doi: 10.1097/ALN.0b013e31819daf31. [PubMed:19352159 ]
  4. 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 ]
  5. Jonsson M, Gurley D, Dabrowski M, Larsson O, Johnson EC, Eriksson LI: Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade. Anesthesiology. 2006 Sep;105(3):521-33. [PubMed:16931985 ]
  6. 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
no
Actions
antagonistpartial agonist
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 ]
Kind
Protein
Organism
Human
Pharmacological action
no
Actions
antagonist
General Function:
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 Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. Habre W, Adamicza A, Lele E, Novak T, Sly PD, Petak F: The involvement of histaminic and muscarinic receptors in the bronchoconstriction induced by myorelaxant administration in sensitized rabbits. Anesth Analg. 2008 Dec;107(6):1899-906. doi: 10.1213/ane.0b013e318186587c. [PubMed:19020136 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. Kao YJ, Le ND: The reversal of profound mivacurium-induced neuromuscular blockade. Can J Anaesth. 1996 Nov;43(11):1128-33. [PubMed:8922768 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23