BENZOCAINE

US Approved OTC

First marketed in 1895

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H11NO2
Molecular Weight	165.1891
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=BLFLLBZGZJTVJG-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/monograph/benzocaine-topical.html
Curator's Comment: description was created based on several sources, including https://www.fda.gov/drugs/drugsafety/ucm250024.htm

Benzocaine is a local anesthetic. It acts by blocking voltage-gated sodium ion channels in nerve endings. Benzocaine is available over-the counter for local anesthesia of oral and pharyngeal mucous membranes (sore throat, cold sores, mouth ulcers, toothache, sore gums, denture irritation), otic pain, and as a local anesthetic for surgical or diagnostic procedures. As a spray, benzocaine is used for temporary relief of pain and itching associated with minor burns, sunburn, minor cuts or scrapes, insect bites, or minor skin irritations. Topical application of benzocaine to gums or mouth may cause rare, but serious and potentially fatal adverse effect methemoglobinemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type 10 subunit alpha 3 Target ID: Q9Y5Y9 Gene ID: 6336.0 Gene Symbol: SCN10A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/19661462	Blocker 530		0.32 mM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sore mouth 2 Sources: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009234/	Palliative	Approved 8307	CEPACOL Approved Use Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
Sore throat 18 Sources: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009234/	Palliative	Approved 8307	CEPACOL Approved Use Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
Canker sores 2 Sources: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009234/	Palliative	Approved 8307	CEPACOL Approved Use Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
Burn 39 Sources: https://www.drugs.com/monograph/benzocaine-topical.html	Palliative	Approved 8307	AMERICAINE Approved Use Self-medication for temporary relief of pain and itching associated with minor burns, sunburn, minor cuts or scrapes, insect bites, or minor skin irritations.
Hemorrhoids 4 Sources: https://www.drugs.com/monograph/benzocaine-topical.html	Palliative	Approved 8307	AMERICAINE HEMORRHOIDAL Approved Use Self-medication for temporary relief of pain and itching associated with hemorrhoids
Otitis media 41 Sources: https://www.drugs.com/cdi/benzocaine-drops.html	Palliative	Approved 8307	OTOCAINE DROPS Approved Use Relieving pain and itching in the ear caused by ear infections.

Doses

Dose	Population	Adverse events
20 % single, topical Dose: 20 % Route: topical Route: single Dose: 20 % Sources: https://pubmed.ncbi.nlm.nih.gov/18971079 https://pubmed.ncbi.nlm.nih.gov/17694687	unhealthy, 17-71 years n = 2 Health Status: unhealthy Age Group: 17-71 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/18971079 https://pubmed.ncbi.nlm.nih.gov/17694687	Other AEs: Methaemoglobinaemia... Other AEs: Methaemoglobinaemia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/18971079 https://pubmed.ncbi.nlm.nih.gov/17694687
8 mg 1 times / 2 hours multiple, oral Dose: 8 mg, 1 times / 2 hours Route: oral Route: multiple Dose: 8 mg, 1 times / 2 hours Sources: https://pubmed.ncbi.nlm.nih.gov/20533760	unhealthy, 49.4 years (range: 18–74 years) n = 246 Health Status: unhealthy Age Group: 49.4 years (range: 18–74 years) Sex: M+F Population Size: 246 Sources: https://pubmed.ncbi.nlm.nih.gov/20533760	Sources: https://pubmed.ncbi.nlm.nih.gov/20533760

AEs

AE	Significance	Dose	Population
Methaemoglobinaemia	2 patients	20 % single, topical Dose: 20 % Route: topical Route: single Dose: 20 % Sources: https://pubmed.ncbi.nlm.nih.gov/18971079 https://pubmed.ncbi.nlm.nih.gov/17694687	unhealthy, 17-71 years n = 2 Health Status: unhealthy Age Group: 17-71 years Sex: F Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/18971079 https://pubmed.ncbi.nlm.nih.gov/17694687

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 985	substrate 1168

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
voltage-gated Na channels 2	CYP1A1 344 CYP1A2 1013 CYP2B6 648 CYP2C19 955 CYP2E1 633 UGT 183

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
voltage-gated Na channels 2	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/19661462/ Page: -	yes

Drug as victim

Target	Modality	Activity
CYP1A1 344	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2D6 1168	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2E1 633	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
UGT 183	substrate 3264 Sources: https://dmd.aspetjournals.org/content/47/3/271 Page: -	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:116735	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:116735
ChemicalBook	CB1217951	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB1217951
ChemicalBook	CB9339022	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9339022
MolPort	MolPort-000-871-526	https://www.molport.com/shop/molecule-link/MolPort-000-871-526
ZINC	ZINC000012358719	http://zinc15.docking.org/substances/ZINC000012358719
eMolecules	476470	https://www.emolecules.com/cgi-bin/more?vid=476470

PubMed

Title	Date	PubMed
Clinical evaluation and comparison of 2 topical anesthetics for pain caused by needle sticks and scaling and root planing.	2001 Apr	11338300
Contact dermatitis in students practicing sports: incidence of rubber sensitisation.	2001 Apr	11273970
From cocaine to ropivacaine: the history of local anesthetic drugs.	2001 Aug	11895133
Pharmacological regulation of gastric acid secretion in the apical membrane of parietal cells; a new target for antisecretory drugs.	2001 Dec	11787764
Drug-induced methemoglobinemia during thoracoscopic lung biopsy.	2001 Feb	11235734
Canister tip orientation and residual volume have significant impact on the dose of benzocaine delivered by Hurricaine spray.	2001 Feb	11159236
Modulation of gastric distension-induced sensations by small intestinal receptors.	2001 Jan	11123197
Reducing children's injection pain: lidocaine patches versus topical benzocaine gel.	2001 Jan-Feb	11242725
Comparison of topical EMLA 5% oral adhesive to benzocaine 20% on the pain experienced during palatal anesthetic infiltration in children.	2001 Jan-Feb	11242723
Effects of pelargonidine and a benzocaine analogue p-diethylaminoethyl benzoate on mitochondrial K(ATP) channel.	2001 Jul	11699869
[The killing of aquarium fish by their owners].	2001 Jul 15-Aug 1	11510375
A potentially fatal effect of topical anesthesia.	2001 Jun 15	11419532
Severe methemoglobinemia on reexposure to benzocaine.	2001 Mar	11331174
Inhibition of m3 muscarinic acetylcholine receptors by local anaesthetics.	2001 May	11325812
Allergic contact dermatitis to cinchocaine.	2001 May	11309035
Diaminodiphenylmethane (DDM): frequency of sensitization, clinical relevance and concomitant positive reactions.	2001 May	11298694
The treatment of oral aphthous ulceration or erosive lichen planus with topical clobetasol propionate in three preparations: a clinical and pilot study on 54 patients.	2001 Nov	11722711
Local lymph node assay with non-radioisotope alternative endpoints.	2002 Aug	12238144
Effects of four anaesthetics on the innate immune response of gilthead seabream (Sparus aurata L.).	2002 Jan	11866130
Effects of anaesthesia on blood gases, acid-base status and ions in the toad Bufo marinus.	2002 Mar	11867289
Benzoate X receptors alpha and beta are pharmacologically distinct and do not function as xenobiotic receptors.	2002 Nov 15	12198127
Efficacy of a wax containing benzocaine in the relief of oral mucosal pain caused by orthodontic appliances.	2002 Oct	12411880
Methemoglobinemia induced by topical benzocaine: a warning for the endoscopist.	2002 Sep	12195332
Effectiveness of 20% benzocaine as a topical anesthetic for intraoral injections.	2003	14959903
Efficacy and tolerability of an intraoral benzocaine patch in the relief of spontaneous toothache pain.	2003	12619262
Spectrophotometric determination of labetalol in pharmaceutical preparations and spiked human urine.	2003 Apr	12727538
Two cases of methemoglobinemia from the use of topical anesthetics.	2003 Apr	12660690
Dangerous in small amounts: ten nondrug substances that cause harm.	2003 Aug	12874566
Lipid-protein interactions and effect of local anesthetics in acetylcholine receptor-rich membranes from Torpedo marmorata electric organ.	2003 Aug 5	12885251
Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory.	2003 Feb	12574744
Evolution of sugars in cider brandy aged in oak barrels: a contribution to its characterization.	2003 Feb 12	12568550
Methemoglobinemia and topical pharyngeal anesthesia.	2003 Jan 2	12510055
Children's preference of benzocaine gel versus the lidocaine patch.	2003 Jul-Aug	13678108
Benzocaine-induced methemoglobinemia.	2003 Mar	12629296
Severe methemoglobinemia after transesophageal echocardiography.	2003 May-Jun	12756430
Tongue entrapment in an aluminum juice can.	2004 Apr	15057180
Contact dermatitis and other skin conditions in instrumental musicians.	2004 Apr 16	15090069
Detection of apple juice concentrate in the manufacture of natural and sparkling cider by means of HPLC chemometric sugar analyses.	2004 Jan 28	14733495
Prospective randomized study of viscous lidocaine versus benzocaine in a GI cocktail for dyspepsia.	2004 Jul	15219296
Acute methemoglobinemia after endoscopy.	2004 May-Jun	15226289

Patents

Sample Use Guides

In Vivo Use Guide

Apply topically to the skin as an aerosol spray, cream, lotion, ointment, or solution.

Route of Administration: Other

In Vitro Use Guide

Benzocaine produced voltage-sensor inhibition in voltage-gated Na+ channel (Nav1.5) expressed in HEK293 cells, and caused large leftward shifts in the V1/2 of the steady-state availability curves aswell as a reduction in Imax with an ED50 of 0.32 mM.

Name

Type

Language

BENZOCAINE

Official Name

English

ETHYL PABA

Official Name

English

ETHYL PABA [INCI]

Common Name

English

BENZOCAINE [VANDF]

Common Name

English

AMINOBENZOIC ACID IMPURITY B [EP IMPURITY]

Common Name

English

SUBCUTIN

Brand Name

English

BENZOCAINE [USP-RS]

Common Name

English

Ethyl 4-aminobenzoate

Systematic Name

English

BENZOCAINUM [WHO-IP LATIN]

Common Name

English

BENZOCAINE [HSDB]

Common Name

English

NSC-4688

Code

English

BABY ANBESOL

Brand Name

English

BENZOCAINE [EP MONOGRAPH]

Common Name

English

AR-01

Code

English

NORCAINE

Brand Name

English

BENZOCAINE [WHO-IP]

Common Name

English

PARATHESINE

Common Name

English

Benzocaine [WHO-DD]

Common Name

English

FLAVAMED

Brand Name

English

BENZOIC ACID, 4-AMINO-, ETHYL ESTER

Common Name

English

ETHYL AMINOBENZOATE

Systematic Name

English

AR01

Code

English

BENZOCAINE [USP MONOGRAPH]

Common Name

English

AMERICAINE

Brand Name

English

NSC-41531

Code

English

PARATHESIN

Brand Name

English

BENZOCAINE [MI]

Common Name

English

4-AMINOBENZOIC ACID ETHYL ESTER

Systematic Name

English

ETHYL P-AMINOBENZOATE

Common Name

English

ETHYL AMINOBENZOATE [JAN]

Common Name

English

ANAESTHESIN

Brand Name

English

BENZOCAINE [MART.]

Common Name

English

benzocaine [INN]

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 346.10