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 537		0.32 mM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Sore mouth 2 Sources: https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009234/	Palliative	Approved 8429	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 8429	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 8429	CEPACOL Approved Use Benzocaine lozenges are used to relieve pain and irritation caused by sore throat, sore mouth, or canker sores.
Burn 40 Sources: https://www.drugs.com/monograph/benzocaine-topical.html	Palliative	Approved 8429	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 8429	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 8429	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 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
voltage-gated Na channels 2	CYP1A1 349 CYP1A2 1054 CYP2B6 664 CYP2C19 991 CYP2E1 667 UGT 192

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
voltage-gated Na channels 2	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19661462/ Page: -	yes

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25010377/ Page: -	yes
UGT 192	substrate 3367 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
The optimization test in the guinea-pig. A method for the predictive evaluation of the contact allergenicity of chemicals.	1975 May	1155304
Pediatric anesthesia in dermatologic surgery: when hand-holding is not enough.	2001 Dec	11849262
Reducing children's injection pain: lidocaine patches versus topical benzocaine gel.	2001 Jan-Feb	11242725
Severe methemoglobinemia on reexposure to benzocaine.	2001 Mar	11331174
Diaminodiphenylmethane (DDM): frequency of sensitization, clinical relevance and concomitant positive reactions.	2001 May	11298694
Fluorescent labeling of drugs and simple organic compounds containing amine functional groups, utilizing dansyl chloride in Na(2)CO(3) buffer.	2001 May-Jun	11755390
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
Methemoglobinemia as a cause of respiratory failure.	2002 Apr	11956408
Analysis of N-glycosylation of phospholipase A2 from venom of individual bees by microbore high-performance liquid chromatography-electrospray mass spectrometry using an ion trap mass spectrometer.	2002 Jan 25	11824812
The antinociceptive and histologic effect of sciatic nerve blocks with 5% butamben suspension in rats.	2002 Mar	11867403
Managing patients with local anesthetic complications using alternative methods.	2002 May-Jun	12174527
Benzoate X receptors alpha and beta are pharmacologically distinct and do not function as xenobiotic receptors.	2002 Nov 15	12198127
[Photocontact dermatitis due to ketoprofen and photosensitization to tetrachlorosalicylanide and to Fenticlor(R)].	2002 Oct	12442124
Putative binding sites for benzocaine on a human cardiac cloned channel (Kv1.5).	2002 Oct	12237171
A study of release mechanisms of different ophthalmic drugs from erodible ocular inserts based on poly(ethylene oxide).	2002 Sep	12191691
Should a mucoadhesive patch (DentiPatch) be used for gingival anesthesia in children?	2002 Winter	12779107
Effectiveness of 20% benzocaine as a topical anesthetic for intraoral injections.	2003	14959903
Suspected methemoglobinemia following awake intubation: one possible effect of benzocaine topical anesthesia--a case report.	2003 Apr	12776639
Two cases of methemoglobinemia from the use of topical anesthetics.	2003 Apr	12660690
The association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens.	2003 Aug	14641358
Lipid-protein interactions and effect of local anesthetics in acetylcholine receptor-rich membranes from Torpedo marmorata electric organ.	2003 Aug 5	12885251
Patch testing with the irritant sodium lauryl sulfate (SLS) is useful in interpreting weak reactions to contact allergens as allergic or irritant.	2003 Feb	12694214
Benzocaine-induced methemoglobinemia: experience from a high-volume transesophageal echocardiography laboratory.	2003 Feb	12574744
Anesthesia of fish with benzocaine does not interfere with comet assay results.	2003 Jan 10	12504765
Tongue entrapment in an aluminum juice can.	2004 Apr	15057180
Effects of the local anesthetic benzocaine on the human erythrocyte membrane and molecular models.	2004 Apr 1	15059670
Prospective randomized study of viscous lidocaine versus benzocaine in a GI cocktail for dyspepsia.	2004 Jul	15219296
Reported adverse event cases of methemoglobinemia associated with benzocaine products.	2004 Jun 14	15197044
Methemoglobinemia: an unusual cause of postoperative cyanosis.	2004 Mar	14981472
Iatrogenic methemoglobinemia from benzocaine spray in trauma.	2004 May	15138963
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