Identification

Summary

Mivacurium is a short-acting non-depolarizing neuromuscular blocking agent used to induce anesthesia during intubation and promote skeletal muscle relaxation during surgery or mechanical ventilation.

Generic Name
Mivacurium
DrugBank Accession Number
DB01226
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 1029.2608
Monoisotopic: 1028.560955278
Chemical Formula
C58H80N2O14
Synonyms
  • Mivacurium
External IDs
  • BW B109OU
  • BW-B109OU

Pharmacology

Indication

For inpatients and outpatients, as an adjunct to general anesthesia, to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.

Pharmacology
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Associated Therapies
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Mivacurium 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 action

Mivacurium 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.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Humans
NMuscarinic acetylcholine receptor M2
antagonist
partial agonist
Humans
NMuscarinic acetylcholine receptor M3
antagonist
Humans
UCholinesteraseNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

The 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 elimination

Not Available

Half-life

The 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.

Clearance

Not Available

Adverse Effects
Adverseeffects
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Toxicity

Overdosage with neuromuscular blocking agents may result in neuromuscular block beyond the time needed for surgery and anesthesia.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-Benzodiazepine1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Mivacurium.
AcetazolamideAcetazolamide may increase the central nervous system depressant (CNS depressant) activities of Mivacurium.
AcetophenazineAcetophenazine may increase the central nervous system depressant (CNS depressant) activities of Mivacurium.
AcetyldigitoxinThe risk or severity of Cardiac Arrhythmia can be increased when Mivacurium is combined with Acetyldigitoxin.
AclidiniumThe risk or severity of adverse effects can be increased when Mivacurium is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Adenosine is combined with Mivacurium.
AgomelatineAgomelatine may increase the central nervous system depressant (CNS depressant) activities of Mivacurium.
AlfentanilThe risk or severity of adverse effects can be increased when Mivacurium is combined with Alfentanil.
AlimemazineAlimemazine may increase the central nervous system depressant (CNS depressant) activities of Mivacurium.
AlloinThe therapeutic efficacy of Alloin can be decreased when used in combination with Mivacurium.
Interactions
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Food Interactions
No interactions found.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Mivacurium chloride600ZG213C3106861-44-3WMSYWJSZGVOIJW-ONUALHDOSA-L
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MivacronSolution2 mg/1mLIntravenousAbbVie Inc.2015-01-302018-12-29US flag
MivacronInjection, solution2 mg/1mLIntravenousHospira, Inc.2010-12-132010-12-14US flag
MivacronLiquid2 mg / mLIntravenousAbbvie1994-12-312012-11-03Canada flag
MivacronInjection, solution2 mg/1mLIntravenousHospira, Inc.2010-12-132010-12-14US flag
Mivacurium ChlorideInjection, solution2 mg/1mLIntravenousSandoz2009-04-302009-08-27US flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Mivacurium ChlorideMivacurium chloride (2 mg/1mL)Injection, solutionIntravenousSandoz2009-04-302009-08-27US flag

Categories

ATC Codes
M03AC10 — Mivacurium chloride
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoquinolines and derivatives
Sub Class
Benzylisoquinolines
Direct Parent
Benzylisoquinolines
Alternative Parents
Tetrahydroisoquinolines / Phenoxy compounds / Anisoles / Methoxybenzenes / Alkyl aryl ethers / Aralkylamines / Fatty acid esters / Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Carboxylic acid esters
show 7 more
Substituents
Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzylisoquinoline / Carbonyl group / Carboxylic acid derivative
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
isoquinolines (CHEBI:6958)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
77D66S9Q93
CAS number
133814-19-4
InChI Key
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[C@H]2CC2=CC(OC)=C(OC)C(OC)=C2)=CC(OC)=C1OC

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 References
Not Available
Human Metabolome Database
HMDB0015357
KEGG Compound
C07550
PubChem Compound
5281042
PubChem Substance
46505071
ChemSpider
4444509
RxNav
30077
ChEBI
6958
ChEMBL
CHEMBL1182833
ZINC
ZINC000150338702
Therapeutic Targets Database
DAP000716
PharmGKB
PA450528
RxList
RxList Drug Page
Wikipedia
Mivacurium_chloride
FDA label
Download (1.5 MB)
MSDS
Download (25.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionKidney Diseases / Prostate Hypertrophy1
4CompletedTreatmentEfficacy and Safety of Mivacurium Chloride for Pediatric Patients1
4CompletedTreatmentIntubations / Newborns / Preterms1
2Unknown StatusTreatmentHepatic dysfunction1
1CompletedTreatmentMuscle Relaxation / Sex1
Not AvailableCompletedNot AvailableNeuromuscular Blockade1
Not AvailableCompletedTreatmentIntubating Conditions / Performance With Respiratory Exercise Device / Postoperative Myalgia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous2 mg/1mL
Injection, solutionIntravenous; Parenteral2 MG/ML
LiquidIntravenous2 mg / mL
SolutionIntravenous2 mg/1mL
Injection, solutionIntravenous
Injection, solutionIntravenous2 mg/ml
InjectionIntravenous
InjectionIntravenous10 mg/5ml
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not 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 FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
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
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. 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. [Article]
  2. 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. [Article]
  3. 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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
Partial agonist
Curator comments
Though Mivacurium has some inhibitory effects on this target, it is not a very potent inhibitor.
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...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. Hou VY, Hirshman CA, Emala CW: Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. Anesthesiology. 1998 Mar;88(3):744-50. [Article]
Kind
Protein
Organism
Humans
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...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
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. [Article]
Kind
Protein
Organism
Humans
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
Uniprot Name
Cholinesterase
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at June 16, 2021 12:30