Identification

Name
Pipecuronium
Accession Number
DB01338
Type
Small Molecule
Groups
Approved
Description

Pipecuronium is a piperazinyl androstane derivative which is a non-depolarizing neuromuscular blocking agent.

Structure
Thumb
Synonyms
  • Pipecurium
  • Pipecuronium
Product Ingredients
IngredientUNIICASInChI Key
Pipecuronium bromideR6ZTY81RE152212-02-9TXWBOBJCRVVBJF-YTGGZNJNSA-L
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ArduanInjection10 mg/1IntravenousOrganon1990-07-262001-09-27Us
International/Other Brands
Arduan
Categories
UNII
1N3O74HM92
CAS number
68399-58-6
Weight
Average: 602.8912
Monoisotopic: 602.477106492
Chemical Formula
C35H62N4O4
InChI Key
OWWLUIWOFHMHOQ-XGHATYIMSA-N
InChI
InChI=1S/C35H62N4O4/c1-24(40)42-32-21-26-9-10-27-28(35(26,4)23-31(32)37-15-19-39(7,8)20-16-37)11-12-34(3)29(27)22-30(33(34)43-25(2)41)36-13-17-38(5,6)18-14-36/h26-33H,9-23H2,1-8H3/q+2/t26-,27+,28-,29-,30-,31-,32-,33-,34-,35-/m0/s1
IUPAC Name
4-[(1S,2S,4S,5S,7S,10R,11S,13S,14R,15S)-5,14-bis(acetyloxy)-13-(4,4-dimethylpiperazin-4-ium-1-yl)-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-4-yl]-1,1-dimethylpiperazin-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)N1CC[N+](C)(C)CC1)N1CC[N+](C)(C)CC1

Pharmacology

Indication

Used as a muscle relaxant during anesthesia and surgical procedures.

Pharmacodynamics

Pipecuronium is a nondepolarizing neuromuscular blocking agent. Neuromuscular blocking agents produce skeletal muscle paralysis by blocking neural transmission at the myoneural junction. The paralysis is selective initially and usually appears in the following muscles consecutively: levator muscles of eyelids, muscles of mastication, limb muscles, abdominal muscles, muscles of the glottis, and finally, the intercostal muscles and the diaphragm. Neuromuscular blocking agents have no clinically significant effect on consciousness or the pain threshold.

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
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

Distribution Normal renal function: 6.22 (range, 1.34 to 10.66) minutes. Renal function impairment: 4.33 (range, 1.69 to 6.17) minutes. Elimination Normal renal function: 1.7 (range, 0.9 to 2.7) hours. The elimination half-life is not altered by hypothermia and bypass. Renal function impairment: 4 (range, 2 to 8.2) hours. [PharmGKB]

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Pipecuronium 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 Pipecuronium is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Pipecuronium is combined with 7-Nitroindazole.
AcepromazineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Pipecuronium is combined with Aceprometazine.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Pipecuronium.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015431
KEGG Compound
C07554
PubChem Compound
50192
PubChem Substance
46508493
ChemSpider
45517
ChEBI
8230
ChEMBL
CHEMBL1201206
Therapeutic Targets Database
DAP000353
PharmGKB
PA164764567
Wikipedia
Pipecuronium
ATC Codes
M03AC06 — Pipecuronium bromide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous10 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility9.5e-05 mg/mLALOGPS
logP-1.4ALOGPS
logP-5.3ChemAxon
logS-6.8ALOGPS
pKa (Strongest Basic)5.31ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area59.08 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity193.04 m3·mol-1ChemAxon
Polarizability72.22 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8906
Blood Brain Barrier+0.6351
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.8501
P-glycoprotein inhibitor IInhibitor0.7487
P-glycoprotein inhibitor IIInhibitor0.5983
Renal organic cation transporterNon-inhibitor0.7112
CYP450 2C9 substrateNon-substrate0.8587
CYP450 2D6 substrateNon-substrate0.7823
CYP450 3A4 substrateSubstrate0.7542
CYP450 1A2 substrateNon-inhibitor0.9065
CYP450 2C9 inhibitorNon-inhibitor0.9152
CYP450 2D6 inhibitorNon-inhibitor0.9059
CYP450 2C19 inhibitorNon-inhibitor0.8819
CYP450 3A4 inhibitorNon-inhibitor0.8232
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9438
Ames testNon AMES toxic0.752
CarcinogenicityNon-carcinogens0.9083
BiodegradationNot ready biodegradable0.9272
Rat acute toxicity2.6004 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9193
hERG inhibition (predictor II)Non-inhibitor0.7647
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 / N-methylpiperazines / Dicarboxylic acids and derivatives / Tetraalkylammonium salts / Trialkylamines / Carboxylic acid esters / Amino acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organic salts
show 4 more
Substituents
Steroid ester / Androstane-skeleton / N-methylpiperazine / N-alkylpiperazine / 1,4-diazinane / Dicarboxylic acid or derivatives / Piperazine / Tetraalkylammonium salt / Quaternary ammonium salt / Amino acid or derivatives
show 18 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
steroid ester (CHEBI:8230)

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. Karpati E, Biro K, Kukorelli T: [Investigation of neuromuscular blocking agents at Richter Ltd]. Acta Pharm Hung. 2002;72(1):37-48. [PubMed:12426786]
  3. Kiss JP, Windisch K, Balla A, Sershen H, Lajtha A: Dual effect of DMPP on the resting release of noradrenaline from rat hippocampal slices. Brain Res Bull. 1997;43(3):257-62. [PubMed:9227834]
  4. Torocsik A, Oberfrank F, Sershen H, Lajtha A, Nemesy K, Vizi ES: Characterization of somatodendritic neuronal nicotinic receptors located on the myenteric plexus. Eur J Pharmacol. 1991 Sep 24;202(3):297-302. [PubMed:1748153]
  5. 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
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. Karpati E, Biro K, Kukorelli T: [Investigation of neuromuscular blocking agents at Richter Ltd]. Acta Pharm Hung. 2002;72(1):37-48. [PubMed:12426786]
  2. Zappi L, Song P, Nicosia S, Nicosia F, Rehder K: Do pipecuronium and rocuronium affect human bronchial smooth muscle? Anesthesiology. 1999 Dec;91(6):1616-21. [PubMed:10598601]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
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. Karpati E, Biro K, Kukorelli T: [Investigation of neuromuscular blocking agents at Richter Ltd]. Acta Pharm Hung. 2002;72(1):37-48. [PubMed:12426786]

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. Simon G, Biro K, Karpati E, Tuba Z: The effect of the steroid muscle relaxant pipecurium bromide on the acetylcholinesterase activity of red blood cells in vitro. Arzneimittelforschung. 1980;30(2a):360-3. [PubMed:6248079]

Drug created on June 30, 2007 12:08 / Updated on November 02, 2018 08:38