RAPACURONIUM

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C37H61N2O4
Molecular Weight	597.8912
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	1

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@H]([C@H](OC(=O)CC)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC[C@@]4([H])C[C@H](OC(C)=O)[C@H](C[C@]34C)N5CCCCC5)[N+]6(CC=C)CCCCC6

InChI

InChIKey=HTIKWNNIPGXLGM-YLINKJIISA-N

InChI=1S/C37H61N2O4/c1-6-20-39(21-12-9-13-22-39)32-24-30-28-15-14-27-23-33(42-26(3)40)31(38-18-10-8-11-19-38)25-37(27,5)29(28)16-17-36(30,4)35(32)43-34(41)7-2/h6,27-33,35H,1,7-25H2,2-5H3/q+1/t27-,28+,29-,30-,31-,32-,33-,35-,36-,37-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20984lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/raplon-drug.htm | https://dailymed.nlm.nih.gov/dailymed/archives/fdaDrugInfo.cfm?archiveid=43578

Rapacuronium bromide (RAPLON), a nondepolarizing neuromuscular blocking agent, is a negative allosteric modulator of muscarinic acetylcholine receptors. Rapacuronium bromide is indicated as an adjunct to general anesthesia to facilitate tracheal intubation and to provide skeletal muscle relaxation during surgical procedures. There were no specific pharmacokinetic studies conducted to examine the drug-drug interactions of RAPLON. Due to the risk of fatal bronchospasm, it was withdrawn from the United States market less than 2 years after its FDA approval.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 169 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038295	Negative Allosteric Modulator 42	4.3 null [pEC50]
Muscarinic acetylcholine receptor M2 121 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038295 \| https://www.ncbi.nlm.nih.gov/pubmed/15618795 \| https://www.ncbi.nlm.nih.gov/pubmed/12657852	Negative Allosteric Modulator 42	4.55 null [pEC50]
Muscarinic acetylcholine receptor M3 159 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038295 \| https://www.ncbi.nlm.nih.gov/pubmed/15618795 \| https://www.ncbi.nlm.nih.gov/pubmed/12657852	Negative Allosteric Modulator 42	4.12 null [pEC50]
Muscarinic acetylcholine receptor M4 86 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038295	Negative Allosteric Modulator 42	9.69 null [pEC50]
Muscarinic acetylcholine receptor M5 62 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20038295	Negative Allosteric Modulator 42	4.21 null [pEC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Skeletal muscle relaxation 17 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020984s003lbl.pdf	Primary		Withdrawn	RAPLON Approved Use RAPLON™ (rapacuronium bromide) for Injection is indicated as an adjunct to general anesthesia to facilitate tracheal intubation, and to provide skeletal muscle relaxation during surgical procedures. Launch Date 9.3484797E11

C_max

Value	Dose	Co-administered	Analyte	Population
7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10500937/	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		RAPACURONIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
160 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10500937/	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		RAPACURONIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
70.3 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10500937/	0.6 mg/kg single, intravenous dose: 0.6 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		RAPACURONIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
27.8 min DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020984s003lbl.pdf	1.5 mg/kg 1 times / day steady-state, intravenous dose: 1.5 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		RAPACURONIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020984s003lbl.pdf	1.5 mg/kg 1 times / day steady-state, intravenous dose: 1.5 mg/kg route of administration: Intravenous experiment type: STEADY-STATE co-administered:		RAPACURONIUM plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	Other AEs: Bronchospasm, Tachycardia... Other AEs: Bronchospasm (3.4%) Tachycardia (1.6%) Injection site reaction (1.1%) Hypotension (0.9%) Airway peak pressure increased (0.6%) Erythematous rash (0.5%) Hypertension (<0.1%) Fever (<0.1%) Nausea and vomiting (<0.1%) Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/

AEs

AE	Significance	Dose	Population
Erythematous rash	0.5%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Airway peak pressure increased	0.6%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Hypotension	0.9%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Injection site reaction	1.1%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Tachycardia	1.6%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Bronchospasm	3.4%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Fever	<0.1%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Hypertension	<0.1%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/
Nausea and vomiting	<0.1%	3 mg/kg single, intravenous Recommended Dose: 3 mg/kg Route: intravenous Route: single Dose: 3 mg/kg Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/	unhealthy, adult n = 1300 Health Status: unhealthy Condition: planned operation Age Group: adult Sex: unknown Population Size: 1300 Sources: https://pubmed.ncbi.nlm.nih.gov/10595867/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 450 31

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 31	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20984lbl.pdf#page=7 Page: 7.0	unlikely

Sourcing

Vendor/Aggregator	ID	URL
Achemtek	0102-014434	http://www.achemtek.com/156137-99-4
Chem Scene	CS-6564	http://www.chemscene.com/156137-99-4.html
Chemspace	CSSS00161189533	https://chem-space.com/CSSS00161189533
Lab Network	LN01313170	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01313170
MedChem Express	HY-16423	https://www.medchemexpress.com/RAPACURONIUM_BROMIDE.html
MolPort	MolPort-006-169-994	https://www.molport.com/shop/molecule-link/MolPort-006-169-994
MuseChem	I008978	https://www.musechem.com/product/I008978.html
MuseChem	M091418	https://www.musechem.com/product/M091418.html
Smolecule	S541060	http://www.smolecule.com/products/s541060
THE BioTek	bt-279759	https://www.thebiotek.com/product/inhibitors/bt-279759
eNovation Chemicals	D676121	https://www.enovationchem.com/ProductDetails.asp?ProductID=D676121

PubMed

Title	Date	PubMed
Time course of action and endotracheal intubating conditions of Org 9487, a new short-acting steroidal muscle relaxant; a comparison with succinylcholine.	1993 Sep	8103650
Preliminary investigations of the clinical pharmacology of three short-acting non-depolarizing neuromuscular blocking agents, Org 9453, Org 9489 and Org 9487.	1994 Mar	7910526
A mechanism for rapacuronium-induced bronchospasm: M2 muscarinic receptor antagonism.	2003 Apr	12657852
Rapacuronium preferentially antagonizes the function of M2 versus M3 muscarinic receptors in guinea pig airway smooth muscle.	2005 Jan	15618795
In silico prediction of blood brain barrier permeability: an Artificial Neural Network model.	2006 Jan-Feb	16426064
Divergence of allosteric effects of rapacuronium on binding and function of muscarinic receptors.	2009 Dec 28	20038295
Determining the potency of neuromuscular blockers: are traditional methods flawed?	2010 Jun	20430764

Patents

Sample Use Guides

In Vivo Use Guide

The adult (1.5 mg/kg), pediatric (2.0 mg/kg), and Cesarean section (2.5 mg/kg)

Route of Administration: Intravenous

In Vitro Use Guide

Effects of 10 uM rapacuronium on the dissociation rate of high-affinity [3H]ACh binding were measured after 60 min preincubation of membranes with 40 nM [3H]ACh. Dissociation was evoked by the addition of unlabeled ACh at a final concentration of 40 uM, either alone or mixed with 10 uM rapacuronium. The slower phase of [3H]ACh dissociation displayed a rate (koff) in the range of 0.112 (M5) to 0.507 (M2) min-1.

Name

Type

Language

RAPACURONIUM

Common Name

English

1-ALLYL-1-(3.ALPHA.,17.BETA.-DIHYDROXY-2.BETA.-PIPERIDINO-5.ALPHA.-ANDROSTAN-16.BETA.-YL)PIPERIDINIUM, 3-ACETATE 17-PROPIONATE

Common Name

English

RAPACURONIUM CATION

Common Name

English

RAPACURONIUM ION

Common Name

English

ANDROSTANE-3,17-DIOL, 2-(1-PIPERIDINYL)-16-(1-(2-PROPENYL)-1-PIPERIDINIUMYL)-, 3-ACETATE 17-PROPANOATE, (2.BETA.,3.ALPHA.,5.ALPHA.,16.BETA.,17.BETA.)-

Common Name

English

RAPACURONIUM [VANDF]

Common Name

English

Code System Code Type Description

DRUG CENTRAL

3520