MIVACURIUM CHLORIDE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1373287 | https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/078562s000lbl.pdf

Mivacurium chloride (Mivacron) is a new benzylisoquinolinium choline-like diester neuromuscular blocking drug with an onset of action at equipotent doses that is comparable to atracurium and vecuronium but slower than succinylcholine. MIVACRON (a mixture of three stereoisomers) 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. MIVACRON is a short-acting neuromuscular blocking agent indicated 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Muscle-type nicotinic acetylcholine receptor 65 Target ID: CHEMBL2362997 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/078562s000lbl.pdf \| http://drugcentral.org/drugcard/1822?q=MIVACURIUM \| https://www.ncbi.nlm.nih.gov/pubmed/19417616	Antagonist 2778		3.69 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Muscle relaxation 3 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/078562s000lbl.pdf	Primary		Approved 8429	MIVACRON Approved Use MIVACRON is a short-acting neuromuscular blocking agent indicated 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. Launch Date 1992

C_max

Value	Dose	Analyte	Population
504 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-CIS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2198 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-TRANS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4486 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, TRANS-TRANS- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1.295 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-CIS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.178 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-TRANS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.932 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, TRANS-TRANS- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
28.5 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-CIS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, CIS-TRANS- plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.4 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9054251/	0.15 mg/kg single, intravenous dose: 0.15 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:	MIVACURIUM, TRANS-TRANS- plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.2 mg/kg single, intravenous Recommended Dose: 0.2 mg/kg Route: intravenous Route: single Dose: 0.2 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020098s018lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Skeletal muscle relaxation during surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020098s018lbl.pdf Page: p.12	Other AEs: Anaphylactic reaction... Other AEs: Anaphylactic reaction (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020098s018lbl.pdf Page: p.12

AEs

AE	Significance	Dose	Population
Anaphylactic reaction	grade 3-5	0.2 mg/kg single, intravenous Recommended Dose: 0.2 mg/kg Route: intravenous Route: single Dose: 0.2 mg/kg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020098s018lbl.pdf Page: p.12	unhealthy Health Status: unhealthy Condition: Skeletal muscle relaxation during surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020098s018lbl.pdf Page: p.12

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1NQXXZ
AN PharmaTech	AN-33846
BOC Sciences	106791-40-6	https://www.bocsci.com/mivacurium-cas-106791-40-6-item-81392.html
ChemMol	49421596	http://www.chemmol.com/chemmol/49421596.html
MuseChem	M012797	https://www.musechem.com/product/M012797.html
MuseChem	M130592	https://www.musechem.com/product/M130592.html
NovoSeek	5281042
OChem	22912	http://www.ocheminc.com/index.php?act=psearch&pid=791M406
PubChem	5281042	https://pubchem.ncbi.nlm.nih.gov/compound/5281042
eNovation Chemicals	D674576	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674576

PubMed

Title	Date	PubMed
Markedly prolonged paralysis after mivacurium in a patient apparently heterozygous for the atypical and usual pseudocholinesterase alleles by conventional biochemical testing.	1997 Feb	9024049
Potentiation of mivacurium by rocuronium is age- and time-dependent: a study in children, adolescents, and young and elderly adults.	1997 Jul	9243359
The effect of mivacurium pretreatment on intra-ocular pressure changes induced by suxamethonium.	1998 May	9659028
Organophosphorus pesticide-induced butyrylcholinesterase inhibition and potentiation of succinylcholine toxicity in mice.	1999	9890196
Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade.	2006 Sep	16931985
Fresh frozen plasma transfusion for reversal of prolonged post-anaesthesia apnoea.	2008 Apr	18399847
Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium.	2014	25054547

Patents

Sample Use Guides

In Vivo Use Guide

Adults Initial Doses Doses of 0.15 mg/kg administered over 5 to 15 seconds, 0.20 mg/kg administered over 30 seconds, or 0.25 mg/kg administered in divided doses (0.15 mg/kg followed in 30 seconds by 0.10 mg/kg) are recommended for facilitation of tracheal intubation for most patients

Route of Administration: Intravenous

In Vitro Use Guide

The left or right atria of rats were removed and suspended in organ baths. Mivacurium was added cumulatively (10(-9)-10(-5) M) in the presence and absence of the nonselective β-blocker propranolol (10(-8) M) and the noradrenaline reuptake inhibitor desipramine (10(-7) M), and heart rate changes were recorded in spontaneously beating right atria. Mivacurium increased developed force in a dose-dependent manner; the increases were significant at 10(-5) M concentration for mivacurium.

Name

Type

Language

MIVACURIUM CHLORIDE

Official Name

English

MIVACURIUM CHLORIDE [USAN]

Common Name

English

mivacurium chloride [INN]

Common Name

English

MIVACURIUM CHLORIDE [ORANGE BOOK]

Common Name

English

MIVACURIUM CHLORIDE [MI]

Common Name

English

BW-B109OU DICHLORIDE

Code

English

BW-1090U DICHLORIDE

Code

English

MIVACURIUM CHLORIDE [MART.]

Common Name

English

BW B109OU DICHLORIDE

Code

English

MIVACURIUM CHLORIDE [VANDF]

Common Name

English

(R)-1,2,3,4-TETRAHYDRO-2-(3-HYDROXYPROPYL)-6,7-DIMETHOXY-2-METHYL-1-(3,4,5-TRIMETHOXYBENZYL)ISOQUINOLINIUM CHLORIDE, (E)-4-OCTENEDIOATE

Common Name

English

MIVACRON

Brand Name

English

Mivacurium chloride [WHO-DD]

Common Name

English

ISOQUINOLINIUM, 2,2'-((1,8-DIOXO-4-OCTENE-1,8-DIYL)BIS(OXY-3,1-PROPANEDIYL))BIS(1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-2-METHYL-1-((3,4,5-TRIMETHOXYPHENYL)METHYL)-, DICHLORIDE, (R-(R*,R*-(E)))-

Common Name

English

ISOQUINOLINIUM, 2,2'-(((4E)-1,8-DIOXO-4-OCTENE-1,8-DIYL)BIS(OXY-3,1-PROPANEDIYL))BIS(1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-2-METHYL-1-((3,4,5-TRIMETHOXYPHENYL)METHYL)-, CHLORIDE (1:2), (1R,1'R)-

Common Name

English

Classification Tree Code System Code

WHO-ATC

M03AC10