Identification

Name
Decamethonium
Accession Number
DB01245  (APRD00696)
Type
Small Molecule
Groups
Approved
Description

Decamethonium is a short acting depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralysis. It is similar to acetylcholine and acts as a partial agonist of the nicotinic acetylcholine receptor.

Structure
Thumb
Synonyms
  • Decamethonium
  • DECAMETHONIUM ion
  • Decamethonum
  • Decamethylenebis(trimethylammonium)
  • N,N,N,N',n',n'-hexamethyl-1,10-decanediaminium
External IDs
Lopac-D-1260
Product Ingredients
IngredientUNIICASInChI Key
Decamethonium bromide55C6RK944K541-22-0HLXQFVXURMXRPU-UHFFFAOYSA-L
International/Other Brands
Syncurine
Categories
UNII
C1CG1S3T2W
CAS number
156-74-1
Weight
Average: 258.4863
Monoisotopic: 258.303499226
Chemical Formula
C16H38N2
InChI Key
MTCUAOILFDZKCO-UHFFFAOYSA-N
InChI
InChI=1S/C16H38N2/c1-17(2,3)15-13-11-9-7-8-10-12-14-16-18(4,5)6/h7-16H2,1-6H3/q+2
IUPAC Name
trimethyl[10-(trimethylazaniumyl)decyl]azanium
SMILES
C[N+](C)(C)CCCCCCCCCC[N+](C)(C)C

Pharmacology

Indication

For use as a skeletal muscle relaxant

Pharmacodynamics

Decamethonium acts as a depolarizing muscle relaxant or neuromuscular blocking agent. It acts as an agonist of nicotinic acetycholine receptors in the motor endplate and causes depolarization. This class of drugs has its effect at the neuromuscular junction by preventing the effects of acetylcholine. Normally, when a nerve stimulus acts to contract a muscle, it releases acetylcholine. The binding of this acetylcholine to receptors causes the muscle to contract. Muscle relaxants play an important role in anesthesia even though they don't provide any pain relief or produce unconsciousness.

Mechanism of action

Binds to the nicotinic acetycholine receptors (by virtue of its similarity to acetylcholine) in the motor endplate and blocks access to the receptors. In the process of binding, the receptor is actually activated - causing a process known as depolarization. Since it is not degraded in the neuromuscular junction, the depolarized membrance remains depolarized and unresponsive to any other impulse, causing muscle paralysis.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
partial agonist
Human
UAcetylcholinesterase
inhibitor
Human
UNeuronal acetylcholine receptor subunit alpha-4Not AvailableHuman
UNeuronal acetylcholine receptor subunit beta-2Not AvailableHuman
Absorption

Rapidly absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

LD50=190 mg/kg (orally in mice). Prolonged apnoea, neuromuscular paralysis and cardiac arrest may occur.

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

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Decamethonium.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Decamethonium.
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Decamethonium.
AcebutololDecamethonium may increase the bradycardic activities of Acebutolol.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Decamethonium.
AcetylcholineThe risk or severity of adverse effects can be increased when Decamethonium is combined with Acetylcholine.
AcetyldigitoxinDecamethonium may increase the arrhythmogenic activities of Acetyldigitoxin.
AcetyldigoxinDecamethonium may increase the arrhythmogenic activities of Acetyldigoxin.
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Decamethonium.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Decamethonium.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015375
KEGG Compound
C11733
PubChem Compound
2968
PubChem Substance
46507737
ChemSpider
2862
BindingDB
50060582
ChEBI
41934
ChEMBL
CHEMBL1190
Therapeutic Targets Database
DAP000378
PharmGKB
PA164747980
HET
DME
Wikipedia
Decamethonium
PDB Entries
1acl / 1maa / 2xud / 3mes / 5e2i / 5e4j / 6ep4
MSDS
Download (56.6 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)268-270 °CNot Available
water solubilitySubstantialNot Available
Predicted Properties
PropertyValueSource
Water Solubility7.04e-06 mg/mLALOGPS
logP-2.8ALOGPS
logP-4.9ChemAxon
logS-7.7ALOGPS
Physiological Charge2ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity106.95 m3·mol-1ChemAxon
Polarizability35.94 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9862
Blood Brain Barrier+0.9444
Caco-2 permeable+0.7036
P-glycoprotein substrateSubstrate0.5439
P-glycoprotein inhibitor INon-inhibitor0.9679
P-glycoprotein inhibitor IINon-inhibitor0.7809
Renal organic cation transporterNon-inhibitor0.5386
CYP450 2C9 substrateNon-substrate0.8398
CYP450 2D6 substrateNon-substrate0.661
CYP450 3A4 substrateNon-substrate0.5423
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9607
CYP450 2D6 inhibitorNon-inhibitor0.9633
CYP450 2C19 inhibitorNon-inhibitor0.9288
CYP450 3A4 inhibitorNon-inhibitor0.9882
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9899
Ames testNon AMES toxic0.9423
CarcinogenicityCarcinogens 0.6778
BiodegradationNot ready biodegradable0.5263
Rat acute toxicity2.6822 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7991
hERG inhibition (predictor II)Non-inhibitor0.6249
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 decamethonium compounds. These are quaternary ammonium compounds containing a trimethyl-(10-trimethylammoniodecyl)ammonium moiety.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Quaternary ammonium salts
Direct Parent
Decamethonium compounds
Alternative Parents
Tetraalkylammonium salts / Organopnictogen compounds / Organic salts / Hydrocarbon derivatives / Amines / Organic cations
Substituents
Decamethonium / Tetraalkylammonium salt / Organopnictogen compound / Hydrocarbon derivative / Organic salt / Amine / Organic cation / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
quaternary ammonium ion (CHEBI:41934)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
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. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. 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]
  3. Lee C, Jones T: Molecular conformation-activity relationship of decamethonium congeners. Br J Anaesth. 2002 May;88(5):692-9. [PubMed:12067008]
  4. Maneckjee R, Minna JD: Opioids induce while nicotine suppresses apoptosis in human lung cancer cells. Cell Growth Differ. 1994 Oct;5(10):1033-40. [PubMed:7848904]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Details
2. Acetylcholinesterase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Robaire B, Kato G: Effects of edrophonium, eserine, decamethonium, d-tubocurarine, and gallamine on the kinetics of membrane-bound and solubilized eel acetylcholinesterase. Mol Pharmacol. 1975 Nov;11(6):722-34. [PubMed:1207670]
  2. Sinha BK, Chignell CF: Synthesis and biological activity of spin-labeled analogs of biotin, hexamethonium, decamethonium, dichlorisoproterenol, and propranolol. J Med Chem. 1975 Jul;18(7):669-73. [PubMed:239236]
  3. Wu CS, Yang JT: Tacrine protection of acetylcholinesterase from inactivation by diisopropylfluorophosphate: a circular dichroism study. Mol Pharmacol. 1989 Jan;35(1):85-92. [PubMed:2913485]
  4. Seto Y, Shinohara T: Structure-activity relationship of reversible cholinesterase inhibitors including paraquat. Arch Toxicol. 1988 Aug;62(1):37-40. [PubMed:3190453]
  5. Hallek M, Szinicz L: Effects of some mono- and bisquaternary ammonium compounds on the reactivatability of soman-inhibited human acetylcholinesterase in vitro. Biochem Pharmacol. 1988 Mar 1;37(5):819-25. [PubMed:3345199]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
competitive antagonist
General Function
Ligand-gated ion channel activity
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 permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Eaton JB, Peng JH, Schroeder KM, George AA, Fryer JD, Krishnan C, Buhlman L, Kuo YP, Steinlein O, Lukas RJ: Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells. Mol Pharmacol. 2003 Dec;64(6):1283-94. [PubMed:14645658]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
competitive antagonist
General Function
Ligand-gated ion channel activity
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 permeabl...
Gene Name
CHRNB2
Uniprot ID
P17787
Uniprot Name
Neuronal acetylcholine receptor subunit beta-2
Molecular Weight
57018.575 Da
References
  1. Eaton JB, Peng JH, Schroeder KM, George AA, Fryer JD, Krishnan C, Buhlman L, Kuo YP, Steinlein O, Lukas RJ: Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells. Mol Pharmacol. 2003 Dec;64(6):1283-94. [PubMed:14645658]

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. Munoz-Delgado E, Vidal CJ: Kinetic behaviour of acetylcholinesterase from muscle microsomal membranes. Biochem Int. 1986 Oct;13(4):625-32. [PubMed:3801037]
  2. Danilov AF: [Inhibition of cholinesterase in the myoneural synapses by decamethonium and ditilin]. Farmakol Toksikol. 1967 Nov-Dec;30(6):664-9. [PubMed:5598433]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:37