Identification

Name
Tetraethylammonium
Accession Number
DB08837
Type
Small Molecule
Groups
Experimental, Investigational
Description

Tetraethylammonium is an experimental drug with no approved indication or marketed formulation. The only marketed drug containing tetraethylammonium was a combination drug called Fosglutamina B6, but this drug has now been discontinued. As an experimental agent, tetraethylammonium is used in its salt forms such as tetraethylammonium chloride and tetraethylammonium bromide. Its mechanism of action is still being investigated, but it is known that tetraethylammonium blocks autonomic ganglia, calcium- and voltage- activated potassium channels, and nicotinic acetylcholine receptors. Because of its inhibitory actions at the autonomic ganglia, tetraethylammonium was thought to be a potential therapeutic vasodilator but serious toxic effects were found. The most common use of tetraethylammonium presently is as a pharmacological research agent that blocks selective potassium channels. Structurally, tetraethylammonium is positively charged due to its central quaternary ammonium.

Structure
Thumb
Synonyms
Not Available
External IDs
NSC-102778 / NSC-156315
Product Ingredients
IngredientUNIICASInChI Key
Tetraethylammonium bromide0435621Z3N71-91-0HWCKGOZZJDHMNC-UHFFFAOYSA-M
Tetraethylammonium chloride8B82Z83XNN56-34-8YMBCJWGVCUEGHA-UHFFFAOYSA-M
Tetraethylammonium hydroxideRA8VU41B1F77-98-5LRGJRHZIDJQFCL-UHFFFAOYSA-M
Tetraethylammonium iodideNot AvailableNot AvailableUQFSVBXCNGCBBW-UHFFFAOYSA-M
Tetraethylammonium phosphateNot Available5574-97-0Not applicable
Categories
UNII
5AV7G7EIEE
CAS number
66-40-0
Weight
Average: 130.2511
Monoisotopic: 130.159574645
Chemical Formula
C8H20N
InChI Key
CBXCPBUEXACCNR-UHFFFAOYSA-N
InChI
InChI=1S/C8H20N/c1-5-9(6-2,7-3)8-4/h5-8H2,1-4H3/q+1
IUPAC Name
tetraethylazanium
SMILES
CC[N+](CC)(CC)CC

Pharmacology

Indication

Tetraethylammonium is an experimental drug with no approved indication.

Pharmacodynamics

Tetraethylammonium is a vasodilator because it blocks autonomic ganglia and prevents signals carrying vasoconstrictor impulses from proceeding.

Mechanism of action

Tetraethylammonium's mechanism of action is still being investigated, but it is known that it blocks autonomic ganglia, calcium- and voltage- activated potassium channels, and nicotinic acetylcholine receptors.

TargetActionsOrganism
UpH-gated potassium channel KcsA
inhibitor
Streptomyces lividans
UNeuronal acetylcholine receptor subunit alpha-9
agonist
inhibitor
Human
UCalcium-activated potassium channel subunit alpha-1
inhibitor
Mouse
UPotassium voltage-gated channel subfamily A member 1
blocker
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Tetraethylammonium is eliminated by active renal tubular secretion by the cation transport system.

Half life
Not Available
Clearance
Not Available
Toxicity

Studies in animals and humans have reported cases of serious muscle paralysis, which can lead to respiratory distress and death.

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

Interactions

Drug Interactions
DrugInteraction
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Tetraethylammonium.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Tetraethylammonium.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Tetraethylammonium.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Acetyl sulfisoxazole is combined with Tetraethylammonium.
AcyclovirThe excretion of Tetraethylammonium can be decreased when combined with Acyclovir.
AmantadineThe serum concentration of Tetraethylammonium can be increased when it is combined with Amantadine.
AmilorideThe serum concentration of Tetraethylammonium can be increased when it is combined with Amiloride.
Aminohippuric acidThe serum concentration of Tetraethylammonium can be increased when it is combined with Aminohippuric acid.
ApalutamideThe serum concentration of Tetraethylammonium can be increased when it is combined with Apalutamide.
ApramycinThe risk or severity of adverse effects can be increased when Apramycin is combined with Tetraethylammonium.
Food Interactions
Not Available

References

General References
  1. GRAHAM AJ: Toxic effects in animals and man after tetraethylammonium bromide. Br Med J. 1950 Aug 5;2(4674):321-2. [PubMed:15434379]
  2. O'Neil, Maryadele J. (2013). The Merck Index : An Encyclopedia of Chemicals, Drugs, and Biologicals (15th ed.). Royal Society of Chemistry, The. [ISBN:978-1849736701]
  3. Allen, Loyd V., Jr. (2012). Remington : The Science and Practice of Pharmacy (22nd ed.). Pharmaceutical Press. [ISBN:978-0857110626]
External Links
KEGG Compound
C07512
PubChem Compound
5413
PubChem Substance
175427115
ChemSpider
5220
BindingDB
50149890
ChEBI
44296
ChEMBL
CHEMBL9324
HET
NET
Wikipedia
Tetraethylammonium
PDB Entries
1a9x / 1bxr / 1c30 / 1c3o / 1ce8 / 1cs0 / 1jdb / 1kee / 1m6v / 1t36
MSDS
Download (37.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentHeavy Menstrual Bleeding1
2TerminatedDiagnosticHyperlipidemias1
3CompletedBasic ScienceProstate Cancer1

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)360 °C or 680 °FFrom MSDS.
water solubilitySoluble in water.From MSDS.
Predicted Properties
PropertyValueSource
Water Solubility0.00277 mg/mLALOGPS
logP-1.2ALOGPS
logP-2.5ChemAxon
logS-4.8ALOGPS
Physiological Charge1ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area0 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity54.9 m3·mol-1ChemAxon
Polarizability17.32 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9176
Blood Brain Barrier+0.9547
Caco-2 permeable+0.7044
P-glycoprotein substrateNon-substrate0.6461
P-glycoprotein inhibitor INon-inhibitor0.9865
P-glycoprotein inhibitor IINon-inhibitor0.9451
Renal organic cation transporterNon-inhibitor0.784
CYP450 2C9 substrateNon-substrate0.8448
CYP450 2D6 substrateNon-substrate0.812
CYP450 3A4 substrateNon-substrate0.6615
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9542
CYP450 2C19 inhibitorNon-inhibitor0.9182
CYP450 3A4 inhibitorNon-inhibitor0.9806
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.901
Ames testNon AMES toxic0.9777
CarcinogenicityCarcinogens 0.8582
BiodegradationNot ready biodegradable0.5794
Rat acute toxicity2.3409 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9107
hERG inhibition (predictor II)Non-inhibitor0.8008
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetraalkylammonium salts. These are organonitrogen compounds containing a quaternary ammonium substituted with four alkyl chains.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Quaternary ammonium salts
Direct Parent
Tetraalkylammonium salts
Alternative Parents
Organopnictogen compounds / Organic salts / Hydrocarbon derivatives / Amines / Organic cations
Substituents
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:44296)

Targets

Kind
Protein
Organism
Streptomyces lividans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cat...
Gene Name
kcsA
Uniprot ID
P0A334
Uniprot Name
pH-gated potassium channel KcsA
Molecular Weight
17693.465 Da
References
  1. Ahern CA, Eastwood AL, Lester HA, Dougherty DA, Horn R: A cation-pi interaction between extracellular TEA and an aromatic residue in potassium channels. J Gen Physiol. 2006 Dec;128(6):649-57. [PubMed:17130518]
  2. Bisset D, Chung SH: Efficacy of external tetraethylammonium block of the KcsA potassium channel: molecular and Brownian dynamics studies. Biochim Biophys Acta. 2008 Oct;1778(10):2273-82. doi: 10.1016/j.bbamem.2008.05.008. Epub 2008 Jun 3. [PubMed:18582434]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
Inhibitor
General Function
Calcium channel activity
Specific Function
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the opening of an ion-conducting channel across the plasm...
Gene Name
CHRNA9
Uniprot ID
Q9UGM1
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-9
Molecular Weight
54806.63 Da
References
  1. Akk G, Steinbach JH: Activation and block of mouse muscle-type nicotinic receptors by tetraethylammonium. J Physiol. 2003 Aug 15;551(Pt 1):155-68. Epub 2003 Jun 24. [PubMed:12824448]
Kind
Protein
Organism
Mouse
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated potassium channel activity
Specific Function
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activati...
Gene Name
Kcnma1
Uniprot ID
Q08460
Uniprot Name
Calcium-activated potassium channel subunit alpha-1
Molecular Weight
134394.8 Da
References
  1. Lang DG, Ritchie AK: Tetraethylammonium blockade of apamin-sensitive and insensitive Ca2(+)-activated K+ channels in a pituitary cell line. J Physiol. 1990 Jun;425:117-32. [PubMed:1698974]
  2. Latorre R, Vergara C, Hidalgo C: Reconstitution in planar lipid bilayers of a Ca2+-dependent K+ channel from transverse tubule membranes isolated from rabbit skeletal muscle. Proc Natl Acad Sci U S A. 1982 Feb;79(3):805-9. [PubMed:6278496]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Blocker
General Function
Voltage-gated potassium channel activity
Specific Function
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the kidney (PubMed:1990381...
Gene Name
KCNA1
Uniprot ID
Q09470
Uniprot Name
Potassium voltage-gated channel subfamily A member 1
Molecular Weight
56465.01 Da
References
  1. Kuzmenkov AI, Vassilevski AA, Kudryashova KS, Nekrasova OV, Peigneur S, Tytgat J, Feofanov AV, Kirpichnikov MP, Grishin EV: Variability of Potassium Channel Blockers in Mesobuthus eupeus Scorpion Venom with Focus on Kv1.1: AN INTEGRATED TRANSCRIPTOMIC AND PROTEOMIC STUDY. J Biol Chem. 2015 May 8;290(19):12195-209. doi: 10.1074/jbc.M115.637611. Epub 2015 Mar 19. [PubMed:25792741]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10. [PubMed:10385678]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxin transporter activity
Specific Function
Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.
Gene Name
SLC22A3
Uniprot ID
O75751
Uniprot Name
Solute carrier family 22 member 3
Molecular Weight
61279.485 Da
References
  1. Wu X, Huang W, Ganapathy ME, Wang H, Kekuda R, Conway SJ, Leibach FH, Ganapathy V: Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol. 2000 Sep;279(3):F449-58. [PubMed:10966924]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Symporter activity
Specific Function
Sodium-ion dependent, low affinity carnitine transporter. Probably transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without...
Gene Name
SLC22A4
Uniprot ID
Q9H015
Uniprot Name
Solute carrier family 22 member 4
Molecular Weight
62154.48 Da
References
  1. Wu X, George RL, Huang W, Wang H, Conway SJ, Leibach FH, Ganapathy V: Structural and functional characteristics and tissue distribution pattern of rat OCTN1, an organic cation transporter, cloned from placenta. Biochim Biophys Acta. 2000 Jun 1;1466(1-2):315-27. [PubMed:10825452]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Symporter activity
Specific Function
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
Molecular Weight
62751.08 Da
References
  1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. [PubMed:10525100]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Enomoto A, Takeda M, Taki K, Takayama F, Noshiro R, Niwa T, Endou H: Interactions of human organic anion as well as cation transporters with indoxyl sulfate. Eur J Pharmacol. 2003 Apr 11;466(1-2):13-20. [PubMed:12679137]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K: Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol. 2007 Jul 15;74(2):359-71. doi: 10.1016/j.bcp.2007.04.010. Epub 2007 Apr 13. [PubMed:17509534]
  2. Yonezawa A, Inui K: Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J Pharmacol. 2011 Dec;164(7):1817-25. doi: 10.1111/j.1476-5381.2011.01394.x. [PubMed:21457222]

Drug created on February 20, 2013 17:57 / Updated on November 02, 2018 08:34