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Identification
NameTetraethylammonium
Accession NumberDB08837
TypeSmall Molecule
GroupsExperimental
DescriptionTetraethylammonium 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
TEA
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Tetraethylammonium bromide
Thumb
  • InChI Key: HWCKGOZZJDHMNC-UHFFFAOYSA-M
  • Monoisotopic Mass: 209.077912292
  • Average Mass: 210.155
DBSALT000173
Tetraethylammonium chloride
Thumb
  • InChI Key: YMBCJWGVCUEGHA-UHFFFAOYSA-M
  • Monoisotopic Mass: 165.128427352
  • Average Mass: 165.704
DBSALT000174
Tetraethylammonium hydroxide
Thumb
  • InChI Key: LRGJRHZIDJQFCL-UHFFFAOYSA-M
  • Monoisotopic Mass: 147.162314299
  • Average Mass: 147.2584
DBSALT000176
Tetraethylammonium iodide
Thumb
  • InChI Key: UQFSVBXCNGCBBW-UHFFFAOYSA-M
  • Monoisotopic Mass: 257.064043065
  • Average Mass: 257.1556
DBSALT000177
Tetraethylammonium phosphate
5574-97-0
ThumbNot applicableDBSALT000178
Categories
UNII5AV7G7EIEE
CAS number66-40-0
WeightAverage: 130.2511
Monoisotopic: 130.159574645
Chemical FormulaC8H20N
InChI KeyInChIKey=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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quaternary ammonium salts. These are compounds containing positively charged polyatomic ion of the structure NR4+, R being an alkyl group or an aryl group.
KingdomOrganic compounds
Super ClassOrganonitrogen compounds
ClassQuaternary ammonium salts
Sub ClassNot Available
Direct ParentQuaternary ammonium salts
Alternative Parents
Substituents
  • Quaternary ammonium salt
  • Hydrocarbon derivative
  • Amine
  • Organic cation
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationTetraethylammonium is an experimental drug with no approved indication.
PharmacodynamicsTetraethylammonium is a vasodilator because it blocks autonomic ganglia and prevents signals carrying vasoconstrictor impulses from proceeding.
Mechanism of actionTetraethylammonium'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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationTetraethylammonium is eliminated by active renal tubular secretion by the cation transport system.
Half lifeNot Available
ClearanceNot Available
ToxicityStudies 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point360 °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 FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (37.4 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).
Gene Name:
kcsA
Uniprot ID:
P0A334
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
agonistinhibitor
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 plasma membrane (PubMed:11752216, PubMed:25282151). The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the ...
Gene Name:
CHRNA9
Uniprot ID:
Q9UGM1
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 activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key ...
Gene Name:
Kcnma1
Uniprot ID:
Q08460
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 ]

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-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine...
Gene Name:
SLC22A1
Uniprot ID:
O15245
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
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, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridiniu...
Gene Name:
SLC22A2
Uniprot ID:
O15244
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
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 the involvement of sodium. Relative uptake activity ratio of carnitine to TEA is 1.78. A key substrate of this transporter seems to be ergothioneine (ET).
Gene Name:
SLC22A4
Uniprot ID:
Q9H015
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 cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.
Gene Name:
SLC22A5
Uniprot ID:
O76082
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, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
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 ]
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Drug created on February 20, 2013 17:57 / Updated on August 17, 2016 12:24