T3DB: Benzocaine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (3)XML

Targets (3)

Record Information

Version

2.0

Creation Date

2009-07-21 20:28:20 UTC

Update Date

2014-12-24 20:25:54 UTC

Accession Number

T3D2980

Identification

Common Name

Benzocaine

Class

Small Molecule

Description

Benzocaine is a surface anesthetic that acts by preventing transmission of impulses along nerve fibers and at nerve endings. Benzocaine is a local anesthetic commonly used as a topical pain reliever. It is the active ingredient in many over-the-counter analgesic ointments. Benzocaine is an ester, a compound made from the organic acid PABA (para-aminobenzoic acid) and ethanol. The process in which this ester is created is known as Fischer esterification.

Compound Type

Amine
Anesthetic
Anesthetic, Local
Antipruritic
Drug
Ester
Ether
Food Toxin
Household Toxin
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(p-(Ethoxycarbonyl)phenylamine
4-(Ethoxycarbonyl)aniline
4-(Ethoxycarbonyl)phenylamine
4-Aminobenzoate
4-Aminobenzoic acid
4-Aminobenzoic acid ethyl ester
4-Carbethoxyaniline
Aethoform
Amben ethyl ester
Americaine
Anacaine
Anaesthan-syngala
Anaesthesin
Anaesthin
Anbesol Baby
Anestezin
Anesthesin
Anesthesine
Anesthone
Baby Anbesol
Benzoak
Benzocaina
Benzocainum
Dermoplast
Diet Ayds
Ethoform
Ethyl 4-aminobenzoate
Ethyl 4-aminobenzoic acid
Ethyl aminobenzoate
Ethyl aminobenzoic acid
Ethyl p-aminobenzenecarboxylate
Ethyl p-aminobenzoate
Ethyl p-aminobenzoic acid
Ethyl p-aminophenylcarboxylate
Ethylester kyseliny p-aminobenzoove
Hurricaine
Identhesin
Keloform
Norcain
Norcaine
Ora-jel
Orabase-B
Orthesin
p-(Ethoxycarbonyl)aniline
p-Aminobenzoate
p-Aminobenzoic acid
p-Aminobenzoic acid ethyl ester
p-Carbethoxyaniline
p-Ethoxycarboxylic aniline
Parathesin
Parathesine
Slim Mint Gum
Solarcaine
Solu H
Topcaine

Chemical Formula

C₉H₁₁NO₂

Average Molecular Mass

165.189 g/mol

Monoisotopic Mass

165.079 g/mol

CAS Registry Number

94-09-7

IUPAC Name

ethyl 4-aminobenzoate

Traditional Name

benzocaine

SMILES

CCOC(=O)C1=CC=C(N)C=C1

InChI Identifier

InChI=1S/C9H11NO2/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6H,2,10H2,1H3

InChI Key

InChIKey=BLFLLBZGZJTVJG-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Benzene and substituted derivatives

Sub Class

Benzoic acids and derivatives

Direct Parent

Benzoic acid esters

Alternative Parents

Substituents

Aminobenzoic acid or derivatives
Benzoate ester
Benzoyl
Aniline or substituted anilines
Amino acid or derivatives
Carboxylic acid ester
Carboxylic acid derivative
Monocarboxylic acid or derivatives
Amine
Organonitrogen compound
Organooxygen compound
Primary amine
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organic oxygen compound
Organic nitrogen compound
Aromatic homomonocyclic compound

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

substituted aniline (CHEBI:116735 )
benzoate ester (CHEBI:116735 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	92°C
Boiling Point	310°C
Solubility	1310 mg/L (at 30°C)
LogP	1.86

Predicted Properties

Property	Value	Source
Water Solubility	2.85 g/L	ALOGPS
logP	2.2	ALOGPS
logP	1.5	ChemAxon
logS	-1.8	ALOGPS
pKa (Strongest Basic)	2.78	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	52.32 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	47.53 m³·mol⁻¹	ChemAxon
Polarizability	17.46 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)	splash10-00dl-0980000000-9bd6d020be04ce49bd3e	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00di-4900000000-9341302295e361a20bfd	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0109-9400000000-8e31c925b871e0f0299e	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-0109-9400000000-c755b4e5336a2867357e	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-01b9-1900000000-a811093acfd0672fece6	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - CI-B (Non-derivatized)	splash10-014i-0900000000-49302e8e4fd5158a36da	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00di-5900000000-dcd2847110af7c87bf18	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00dl-0980000000-9bd6d020be04ce49bd3e	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00di-3900000000-8d1e571ebb0276875b64	2017-08-28	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-00kr-0900000000-b54aebb77e7a69ada07c	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)	splash10-014i-5900000000-ce90658bd0fc66df820d	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)	splash10-03xu-9100000000-5179b7804d2c59e71aa4	2012-07-25	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI RMU-7M) , Positive	splash10-00di-4900000000-9341302295e361a20bfd	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI RMU-7) , Positive	splash10-0109-9400000000-8e31c925b871e0f0299e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI RMU-6D) , Positive	splash10-0109-9400000000-c755b4e5336a2867357e	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (HITACHI M-60) , Positive	splash10-01b9-1900000000-57d39b512bc5bdbb4987	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - CI-B (HITACHI M-60) , Positive	splash10-014i-0900000000-49302e8e4fd5158a36da	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - EI-B (JEOL JMS-DX-300) , Positive	splash10-00di-5900000000-dcd2847110af7c87bf18	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positive	splash10-014i-0900000000-a0f10abbe67842c2c958	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positive	splash10-00du-5900000000-43a89461a4d9cc5d1409	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positive	splash10-00dl-9600000000-049e2653cbbf24aaf010	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positive	splash10-002f-9100000000-6fbc7720b326773643af	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positive	splash10-00ou-9000000000-d7f7622c3a270c5ffcbb	2012-08-31	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-qTof , Positive	splash10-000i-5900100000-72ac4bcb64db0d25261e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-014i-0900000000-e061a0f4172b47a8bd22	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-00du-5900000000-54757e57c91d3eaa1976	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-00dl-9600000000-049e2653cbbf24aaf010	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-002f-9100000000-e16fc2db7a632fc6f4da	2017-09-14	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-014j-0900000000-4479c2a548f4aa1aa697	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00xr-0900000000-45723c7ad554a9d56bd1	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9300000000-fab7bee6cbcfbc918d9c	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-03di-1900000000-477a27b8617485132384	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-03xr-3900000000-df3eaaf30a4e906fb038	2017-07-26	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00kf-9400000000-e9f4c1de93ac2ce072b4	2017-07-26	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00xr-6900000000-0594451f3b181ab3c883	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, CDCl₃, experimental)	Not Available	2012-12-05	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 90 MHz, CDCl₃, experimental)	Not Available	2014-09-20	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 25.16 MHz, CDCl₃, experimental)	Not Available	2014-09-23	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-24	View Spectrum
2D NMR	[¹H, ¹³C]-HSQC NMR Spectrum (2D, 600 MHz, CDCl₃, experimental)	Not Available	2012-12-05	View Spectrum

Toxicity Profile

Route of Exposure

Topical; oral

Mechanism of Toxicity

Benzocaine binds to sodium channels and reversibly stabilizes the neuronal membrane which decreases its permeability to sodium ions. Depolarization of the neuronal membrane is inhibited thereby blocking the initiation and conduction of nerve impulses.

Metabolism

Hepatic (to a lesser extent) and plasma via hydrolysis by cholinesterase. Excretion trhough urine (as metabolites) (5)

Toxicity Values

LD50: 3040 mg/kg (Oral, Rat) (1)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Local anesthetic commonly used as a topical pain reliever. Benzocaine is used as a key ingredient in numerous pharmecuticals: Phenazone, an anti-inflammatory; some glycerol-based ear medications for use in removing excess wax as well as relieving ear conditions such as Otitis Media and swimmers ear; some previous diet products such as Ayds; some condoms designed to prevent premature ejaculation. Benzocaine acts to desensitize the penis, and theoretically allows an erection to be maintained. [Wikipedia]

Minimum Risk Level

Not Available

Health Effects

Allergic reactions occur with ester local anaesthetics (like benzocaine) because of the PABA structure. Benzocaine also is a well-known cause of methemoglobinemia. [Wikipedia]. Methemoglobinemia has been reported with benzocaine in oral overdose. (5)

Symptoms

Not Available

Treatment

Treatment is primarily symptomatic and supportive; termination of anesthesia by pneumatic tourniquet inflation should be attempted when the agent is administered by infiltration or regional injection. Methemoglobinemia may be treated with methylene blue, 1-2 mg/kg I.V. infused over several minutes. Seizures commonly respond to diazepam, while hypotension responds to I.V. fluids and Trendelenburg positioning. Bradyarrhythmias (when the heart rate is <60) can be treated with I.V., I.M., or SubQ atropine 15 mcg/kg. With the development of metabolic acidosis, I.V. sodium bicarbonate 0.5-2 mEq/kg and ventilatory assistance should be instituted. (5)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

116735

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Benzocaine

PDB ID

Not Available

ACToR ID

1756

Wikipedia Link

Benzocaine

References

Synthesis Reference

Not Available

MSDS

Link

General References

Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
Bong CL, Hilliard J, Seefelder C: Severe methemoglobinemia from topical benzocaine 7.5% (baby orajel) use for teething pain in a toddler. Clin Pediatr (Phila). 2009 Mar;48(2):209-11. doi: 10.1177/0009922808324491. Epub 2008 Oct 3. [18836057 ]
FENTON PF, COWGILL GR, STONE MA, JUSTICE DH: The nutrition of the mouse. VIII. Studies on pantothenic acid, biotin, inositol and paminobenzoic acid. J Nutr. 1950 Oct;42(2):257-69. [14795275 ]
Drugs.com [Link]
University Of Maryland- Medical Center: Fact Sheet for Benzocaine [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Sodium channel protein type 10 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:: SCN10A
Uniprot ID:: Q9Y5Y9
Molecular Weight:: 220623.605 Da

References

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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. [17016423 ]

Target Details

2. Bile acid receptor

General Function:: Zinc ion binding
Specific Function:: Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:: NR1H4
Uniprot ID:: Q96RI1
Molecular Weight:: 55913.915 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	3.91 uM	OT_SRC1_SRC1FXR_1440	Odyssey Thera

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Target Details

3. Retinoic acid receptor RXR-alpha

General Function:: Zinc ion binding
Specific Function:: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid. RXRA serves as a common heterodimeric partner for a number of nuclear receptors. The RXR/RAR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. In the absence of ligand, the RXR-RAR heterodimers associate with a multiprotein complex containing transcription corepressors that induce histone acetylation, chromatin condensation and transcriptional suppression. On ligand binding, the corepressors dissociate from the receptors and associate with the coactivators leading to transcriptional activation. The RXRA/PPARA heterodimer is required for PPARA transcriptional activity on fatty acid oxidation genes such as ACOX1 and the P450 system genes.
Gene Name:: RXRA
Uniprot ID:: P19793
Molecular Weight:: 50810.835 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
AC50	9.62 uM	OT_NURR1_NURR1RXRa_1440	Odyssey Thera

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

Benzocaine (T3D2980)

Structure for T3D2980: Benzocaine

Targets

References

Binding/Activity Constants

References

Binding/Activity Constants

References