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Record Information
Version2.0
Creation Date2009-07-21 20:28:20 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2980
Identification
Common NameBenzocaine
ClassSmall Molecule
DescriptionBenzocaine 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
Thumb
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 FormulaC9H11NO2
Average Molecular Mass165.189 g/mol
Monoisotopic Mass165.079 g/mol
CAS Registry Number94-09-7
IUPAC Nameethyl 4-aminobenzoate
Traditional Namebenzocaine
SMILESCCOC(=O)C1=CC=C(N)C=C1
InChI IdentifierInChI=1S/C9H11NO2/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6H,2,10H2,1H3
InChI KeyInChIKey=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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzoic 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 FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point92°C
Boiling Point310°C
Solubility1310 mg/L (at 30°C)
LogP1.86
Predicted Properties
PropertyValueSource
Water Solubility2.85 g/LALOGPS
logP2.2ALOGPS
logP1.5ChemAxon
logS-1.8ALOGPS
pKa (Strongest Basic)2.78ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area52.32 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity47.53 m³·mol⁻¹ChemAxon
Polarizability17.46 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-00dl-0980000000-9bd6d020be04ce49bd3e2014-06-16View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-4900000000-9341302295e361a20bfd2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0109-9400000000-8e31c925b871e0f0299e2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0109-9400000000-c755b4e5336a2867357e2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-01b9-1900000000-a811093acfd0672fece62017-09-12View Spectrum
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-014i-0900000000-49302e8e4fd5158a36da2017-09-12View Spectrum
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00di-5900000000-dcd2847110af7c87bf182017-09-12View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dl-0980000000-9bd6d020be04ce49bd3e2017-09-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-3900000000-8d1e571ebb0276875b642017-08-28View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-00kr-0900000000-b54aebb77e7a69ada07c2012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-014i-5900000000-ce90658bd0fc66df820d2012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-03xu-9100000000-5179b7804d2c59e71aa42012-07-25View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-7M) , Positivesplash10-00di-4900000000-9341302295e361a20bfd2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-7) , Positivesplash10-0109-9400000000-8e31c925b871e0f0299e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI RMU-6D) , Positivesplash10-0109-9400000000-c755b4e5336a2867357e2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-60) , Positivesplash10-01b9-1900000000-57d39b512bc5bdbb49872012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - CI-B (HITACHI M-60) , Positivesplash10-014i-0900000000-49302e8e4fd5158a36da2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - EI-B (JEOL JMS-DX-300) , Positivesplash10-00di-5900000000-dcd2847110af7c87bf182012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-014i-0900000000-a0f10abbe67842c2c9582012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-00du-5900000000-43a89461a4d9cc5d14092012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-00dl-9600000000-049e2653cbbf24aaf0102012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-002f-9100000000-6fbc7720b326773643af2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-00ou-9000000000-d7f7622c3a270c5ffcbb2012-08-31View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-5900100000-72ac4bcb64db0d25261e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-014i-0900000000-e061a0f4172b47a8bd222017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00du-5900000000-54757e57c91d3eaa19762017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-00dl-9600000000-049e2653cbbf24aaf0102017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-002f-9100000000-e16fc2db7a632fc6f4da2017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014j-0900000000-4479c2a548f4aa1aa6972017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00xr-0900000000-45723c7ad554a9d56bd12017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9300000000-fab7bee6cbcfbc918d9c2017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-1900000000-477a27b86174851323842017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03xr-3900000000-df3eaaf30a4e906fb0382017-07-26View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-9400000000-e9f4c1de93ac2ce072b42017-07-26View Spectrum
MSMass Spectrum (Electron Ionization)splash10-00xr-6900000000-0594451f3b181ab3c8832014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, CDCl3, experimental)Not Available2012-12-05View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-24View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, CDCl3, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureTopical; oral
Mechanism of ToxicityBenzocaine 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.
MetabolismHepatic (to a lesser extent) and plasma via hydrolysis by cholinesterase. Excretion trhough urine (as metabolites) (5)
Toxicity ValuesLD50: 3040 mg/kg (Oral, Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesLocal 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 LevelNot Available
Health EffectsAllergic 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)
SymptomsNot Available
TreatmentTreatment 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
DrugBank IDDB01086
HMDB IDHMDB04992
PubChem Compound ID2337
ChEMBL IDCHEMBL278172
ChemSpider ID13854242
KEGG IDC07527
UniProt IDNot Available
OMIM ID
ChEBI ID116735
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBenzocaine
PDB IDNot Available
ACToR ID1756
Wikipedia LinkBenzocaine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. Drugs.com [Link]
  5. University Of Maryland- Medical Center: Fact Sheet for Benzocaine [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [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. [17016423 ]
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
TypeValueAssay TypeAssay Source
AC503.91 uMOT_SRC1_SRC1FXR_1440Odyssey Thera
References
  1. 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 ]
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
TypeValueAssay TypeAssay Source
AC509.62 uMOT_NURR1_NURR1RXRa_1440Odyssey Thera
References
  1. 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 ]