Identification

Name
Pancuronium
Accession Number
DB01337
Type
Small Molecule
Groups
Approved
Description

A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than curare but has less effect on the circulatory system and on histamine release.

Structure
Thumb
Synonyms
  • Bromure de pancuronium
  • Bromuro de pancuronio
  • Pancuronium
Product Ingredients
IngredientUNIICASInChI Key
Pancuronium bromideU9LY9Y75X215500-66-0NPIJXCQZLFKBMV-YTGGZNJNSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pancuronium Bromide - Liq IV 1mg/mlLiquid1 mgIntravenousSandoz Canada Incorporated1995-12-31Not applicableCanada
Pancuronium Bromide - Liq IV 2mg/mlLiquid2 mgIntravenousSandoz Canada Incorporated1996-12-31Not applicableCanada
Pancuronium Bromide 1mg/mlSolution1 mgIntravenousHospira, Inc.1996-10-24Not applicableCanada
Pancuronium Bromide 2mg/mlSolution2 mgIntravenousHospira, Inc.1995-12-31Not applicableCanada
Pavulon Inj 1mg/mlLiquid1 mgIntravenousOrganon Canada Ltd Ltee1979-12-311997-08-18Canada
Pavulon Inj 2mg/mlLiquid2 mgIntravenousOrganon Canada Ltd Ltee1973-12-311997-08-18Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pancuronium BromideInjection, solution1 mg/1mLIntravenousHospira, Inc.2005-10-11Not applicableUs
Pancuronium BromideInjection, solution2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.1990-08-012012-07-31Us
Pancuronium BromideInjection, solution1 mg/1mLIntravenousTeva Parenteral Medicines, Inc.1990-08-012012-11-30Us
Pancuronium BromideInjection, solution2 mg/1mLIntravenousTeva Parenteral Medicines, Inc.1990-08-012012-11-30Us
International/Other Brands
Mioblock / Pavulon
Categories
UNII
J76UF062FS
CAS number
Not Available
Weight
Average: 572.8619
Monoisotopic: 572.455308418
Chemical Formula
C35H60N2O4
InChI Key
GVEAYVLWDAFXET-XGHATYIMSA-N
InChI
InChI=1S/C35H60N2O4/c1-24(38)40-32-21-26-13-14-27-28(35(26,4)23-31(32)37(6)19-11-8-12-20-37)15-16-34(3)29(27)22-30(33(34)41-25(2)39)36(5)17-9-7-10-18-36/h26-33H,7-23H2,1-6H3/q+2/t26-,27+,28-,29-,30-,31-,32-,33-,34-,35-/m0/s1
IUPAC Name
1-[(1S,2S,4S,5S,7S,10R,11S,13S,14R,15S)-5,14-bis(acetyloxy)-2,15-dimethyl-13-(1-methylpiperidin-1-ium-1-yl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-4-yl]-1-methylpiperidin-1-ium
SMILES
[H][C@@]12C[C@@H]([C@H](OC(C)=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])C[C@H](OC(C)=O)[C@H](C[C@]12C)[N+]1(C)CCCCC1)[N+]1(C)CCCCC1

Pharmacology

Indication

Used as a muscle relaxant during anesthesia and surgical procedures.

Associated Therapies
Pharmacodynamics

Pancuronium is a typical non-depolarising curare-mimetic muscle relaxant. It acts as a competitive acetylcholine antagonist on neuromuscular junctions, displacing acetylcholine (hence competitive) from its post-synaptic nicotinic acetylcholine receptors. It is, unlike suxamethonium, a non-depolarising agent, which means, that it causes no spontaneous depolarisations upon association with the nicotinic receptor in neuromuscular junction, thus producing no muscle fasciculations upon administration. Pancuronium has no hormonal activity. It exerts slight vagolytic activity (i.e. diminishing activity of the vagus nerve) and no ganglioplegic (i.e., blocking ganglions) activity.

Mechanism of action

Nondepolarizing neuromuscular blocking agents inhibit neuromuscular transmission by competing with acetylcholine for the cholinergic receptors of the motor end plate, thereby reducing the response of the end plate to acetylcholine. This type of neuromuscular block is usually antagonized by anticholinesterase agents.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
UMuscarinic acetylcholine receptor M2
antagonist
Human
UMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption
Not Available
Volume of distribution
  • 241 to 280 mL/kg
Protein binding

77 to 91%

Metabolism

Hepatic.

Route of elimination
Not Available
Half life

1.5 to 2.7 hours.

Clearance
  • Plasma cl=1.1–1.9 mL/minute/kg
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(2-benzhydryloxyethyl)diethyl-methylammonium iodideThe risk or severity of adverse effects can be increased when Pancuronium is combined with (2-benzhydryloxyethyl)diethyl-methylammonium iodide.
1,10-PhenanthrolineThe therapeutic efficacy of Pancuronium can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Pancuronium is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineThe therapeutic efficacy of Pancuronium can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Pancuronium is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Pancuronium is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Pancuronium is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Pancuronium is combined with 5-methoxy-N,N-dimethyltryptamine.
6-O-benzylguanineThe therapeutic efficacy of Pancuronium can be decreased when used in combination with 6-O-benzylguanine.
7-DeazaguanineThe therapeutic efficacy of Pancuronium can be decreased when used in combination with 7-Deazaguanine.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015430
KEGG Compound
C07551
PubChem Compound
441289
PubChem Substance
46506118
ChemSpider
390052
ChEBI
7907
ChEMBL
CHEMBL185073
Therapeutic Targets Database
DAP000123
PharmGKB
PA450771
IUPHAR
4001
Guide to Pharmacology
GtP Drug Page
Wikipedia
Pancuronium
ATC Codes
M03AC01 — Pancuronium
AHFS Codes
  • 12:20.20 — Neuromuscular Blocking Agents

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Baxter International Inc.
  • Elkins-Sinn Inc.
  • Hospira Inc.
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Injection, solutionIntravenous1 mg/1mL
Injection, solutionIntravenous2 mg/1mL
SolutionIntravenous1 mg
SolutionIntravenous2 mg
LiquidIntravenous1 mg
LiquidIntravenous2 mg
Prices
Unit descriptionCostUnit
Pancuronium 2 mg/ml vial2.59USD ml
Pancuronium 1 mg/ml vial0.13USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)215 °CPhysProp
water solubility5E+005 mg/LMERCK INDEX (1996)
Predicted Properties
PropertyValueSource
Water Solubility3.08e-06 mg/mLALOGPS
logP1.04ALOGPS
logP-3.3ChemAxon
logS-8.3ALOGPS
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area52.6 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity185.22 m3·mol-1ChemAxon
Polarizability69.44 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8913
Blood Brain Barrier+0.878
Caco-2 permeable+0.5457
P-glycoprotein substrateSubstrate0.77
P-glycoprotein inhibitor IInhibitor0.6962
P-glycoprotein inhibitor IIInhibitor0.6508
Renal organic cation transporterNon-inhibitor0.6862
CYP450 2C9 substrateNon-substrate0.8382
CYP450 2D6 substrateNon-substrate0.7638
CYP450 3A4 substrateSubstrate0.742
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9229
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9368
Ames testNon AMES toxic0.7499
CarcinogenicityNon-carcinogens0.9265
BiodegradationNot ready biodegradable0.8557
Rat acute toxicity2.6653 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9021
hERG inhibition (predictor II)Non-inhibitor0.7784
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid esters
Direct Parent
Steroid esters
Alternative Parents
Androstane steroids / Piperidines / Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Carboxylic acid esters / Azacyclic compounds / Organopnictogen compounds / Organic salts / Organic oxides / Hydrocarbon derivatives
show 3 more
Substituents
Steroid ester / Androstane-skeleton / Dicarboxylic acid or derivatives / Piperidine / Quaternary ammonium salt / Tetraalkylammonium salt / Carboxylic acid ester / Organoheterocyclic compound / Carboxylic acid derivative / Azacycle
show 12 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
acetate ester, steroid ester (CHEBI:7907)

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
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. 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]
  2. Dilger JP, Vidal AM, Liu M, Mettewie C, Suzuki T, Pham A, Demazumder D: Roles of amino acids and subunits in determining the inhibition of nicotinic acetylcholine receptors by competitive antagonists. Anesthesiology. 2007 Jun;106(6):1186-95. [PubMed:17525594]
  3. 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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. Milchert M, Spassov A, Meissner K, Nedeljkov V, Lehmann C, Wendt M, Loster BW, Mazurkiewicz-Janik M, Gedrange T, Pavlovic D: Skeletal muscle relaxants inhibit rat tracheal smooth muscle tone in vitro. J Physiol Pharmacol. 2009 Dec;60 Suppl 8:5-11. [PubMed:20400785]
  2. Cembala TM, Forde SC, Appadu BL, Lambert DG: Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors. Eur J Pharmacol. 2007 Aug 13;569(1-2):37-40. Epub 2007 May 22. [PubMed:17588565]
  3. Okanlami OA, Fryer AD, Hirshman C: Interaction of nondepolarizing muscle relaxants with M2 and M3 muscarinic receptors in guinea pig lung and heart. Anesthesiology. 1996 Jan;84(1):155-61. [PubMed:8572329]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Milchert M, Spassov A, Meissner K, Nedeljkov V, Lehmann C, Wendt M, Loster BW, Mazurkiewicz-Janik M, Gedrange T, Pavlovic D: Skeletal muscle relaxants inhibit rat tracheal smooth muscle tone in vitro. J Physiol Pharmacol. 2009 Dec;60 Suppl 8:5-11. [PubMed:20400785]
  2. Okanlami OA, Fryer AD, Hirshman C: Interaction of nondepolarizing muscle relaxants with M2 and M3 muscarinic receptors in guinea pig lung and heart. Anesthesiology. 1996 Jan;84(1):155-61. [PubMed:8572329]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Stovner J, Oftedal N, Holmboe J: The inhibition of cholinesterases by pancuronium. Br J Anaesth. 1975 Sep;47(9):949-54. [PubMed:1191483]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Secondary active organic cation transmembrane transporter activity
Specific Function
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnico...
Gene Name
SLC22A1
Uniprot ID
O15245
Uniprot Name
Solute carrier family 22 member 1
Molecular Weight
61153.345 Da
References
  1. Zhang L, Dresser MJ, Gray AT, Yost SC, Terashita S, Giacomini KM: Cloning and functional expression of a human liver organic cation transporter. Mol Pharmacol. 1997 Jun;51(6):913-21. [PubMed:9187257]
  2. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H: Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem. 1996 Dec 20;271(51):32599-604. [PubMed:8955087]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
References
  1. Gorboulev V, Ulzheimer JC, Akhoundova A, Ulzheimer-Teuber I, Karbach U, Quester S, Baumann C, Lang F, Busch AE, Koepsell H: Cloning and characterization of two human polyspecific organic cation transporters. DNA Cell Biol. 1997 Jul;16(7):871-81. [PubMed:9260930]

Drug created on June 30, 2007 12:07 / Updated on October 21, 2018 20:31