:Benzocaine

Benzocaine is indicated to treat a variety of pain-related conditions. It may be used for:

• Local anesthesia of oral and pharyngeal mucous membranes (sore throat, cold sores, mouth ulcers, toothache, sore gums, denture irritation)AHFS Drug Information 2007. McEvoy GK, ed. Benzocaine. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2844-5.
• Otic pain (earache)
• Surgical or procedural local anesthesiaSultan Healthcare. Topex metered spray (benzocaine 20%) prescribing information. Englewood, NJ; 2006.
• Relief of skin pain caused by sunburn, ingrown toenails, hemorrhoids, [https://www.drugs.com/mtm/benzocaine-topical.html Benzocaine topical]

Examples of combination medications of benzocaine include:

• Antipyrine-benzocaine otic consists of antipyrine and benzocaine, and is used to relieve ear pain and remove earwax.{{Cite web |title=Antipyrine-Benzocaine Otic: MedlinePlus Drug Information |url=https://medlineplus.gov/druginfo/meds/a607073.html#:~:text=Antipyrine%20and%20benzocaine%20otic%20is,class%20of%20medications%20called%20analgesics. |access-date=March 28, 2023 |website=medlineplus.gov |language=en}}
• Cepacol consists of menthol and benzocaine, and is used to treat sore throat.{{Cite web |title=Cepacol Sore Throat (Benzocaine-Menthol) Mucous Membrane: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD |url=https://www.webmd.com/drugs/2/drug-164108/cepacol-sore-throat-benzocaine-menthol-mucous-membrane/details |access-date=March 28, 2023 |website=www.webmd.com |language=en}}
• A solution of benzocaine and menthol is marketed for the treatment of bee stings, mosquito bites, jellyfish stings, and other insect bites[https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b8bd9280-f20a-4b2a-aef7-a0ba7b3b8701 STING-KILL - benzocaine and menthol solution]

File:Jiffy Toothache Drops bottle.jpg

Benzocaine is used as a key ingredient in numerous pharmaceuticals:

• Some glycerol-based ear medications for use in removing excess wax as well as relieving ear conditions such as otitis media and swimmer's ear.
• Some previous diet products such as Ayds.
• Some condoms designed to prevent premature ejaculation. Benzocaine largely inhibits sensitivity on the penis, and can allow for an erection to be maintained longer (in a continuous act) by delaying ejaculation. Conversely, an erection will also fade faster if stimulus is interrupted.{{cite news| url=http://news.bbc.co.uk/1/hi/health/2049202.stm | work=BBC News | title='Longer-lasting' condom launched | date=June 17, 2002}}{{cite news| url=https://www.nytimes.com/2002/12/15/magazine/15ENDU.html | work=The New York Times | vauthors = Garner D | title=Endurance Condoms | date=December 15, 2002}}
• Benzocaine mucoadhesive patches have been used in reducing orthodontic pain.{{cite journal | vauthors = Eslamian L, Borzabadi-Farahani A, Edini HZ, Badiee MR, Lynch E, Mortazavi A | title = The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study | journal = Acta Odontologica Scandinavica | volume = 71 | issue = 5 | pages = 1168–1173 | date = September 2013 | pmid = 23301559 | doi = 10.3109/00016357.2012.757358 | s2cid = 22561192 }}
• In Poland it is included, together with menthol and zinc oxide, in the liquid powder (not to be confused with the liquid face powder) used mainly after mosquito bites. Today's ready-made Pudroderm{{cite web|title=Produkty {{!}} PUDRODERM|url=http://www.pampa.com.pl/page.php?cat=produkty&doc=pudroderm|access-date=May 9, 2014|language=pl|archive-url=https://web.archive.org/web/20161018103519/http://pampa.com.pl/page.php?cat=produkty&doc=pudroderm|archive-date=October 18, 2016|url-status=dead}} was once used there as pharmaceutical compound.

Benzocaine can come in a variety of preparations including:

Oral preparations:

• Lozenges (ex. Cepacol, Mycinettes){{cite web|url=http://www.cepacol.com/ |title=Cepacol |publisher=Cepacol.com |access-date=June 2, 2015}}{{failed verification|date=September 2020}}
• Throat Spray (ex. Ultra Chloraseptic){{Cite web|url=https://www.medicines.org.uk/emc/product/5708/smpc|title=Ultra Chloraseptic Anaesthetic Throat Spray 0.71% - Summary of Product Characteristics (SmPC) - (eMC)|website=www.medicines.org.uk|access-date=May 5, 2018|archive-date=May 5, 2018|archive-url=https://web.archive.org/web/20180505205738/https://www.medicines.org.uk/emc/product/5708/smpc|url-status=dead}}

Topical preparations:

• Aerosol (ex. Topex){{cite web|url=http://www.sultanhc.com/sw/swchannel/productcatalogcf_v2/internet/model.asp?ProductMasterID=285313&ParentID=215728&SWID=1 |title=Topex Metered Spray-Sultan Healthcare |publisher=Sultanhc.com |access-date=June 2, 2015}}{{failed verification|date=September 2020}}
• Gel (ex. Orajel, Kank-A){{cite web|url=http://www.orajel.com/ |title=Orajel - Oral Care for the Whole Family |publisher=Orajel.com |date=May 11, 2015 |access-date=June 2, 2015}}{{failed verification|date=September 2020}} {{Cite web |title=Kank-A {{!}} Canker Sore Treatment & Pain Relief |url=https://kank-a.com/ |access-date=November 29, 2023 |language=en-US}}
• Paste (ex. Orabase){{cite web|url=http://www.colgateprofessional.com/products/colgate-orabase-paste-with-benzocaine/overview |title=Colgate Orabase Paste with Benzocaine | Indications | Dental Products |publisher=Colgateprofessional.com |access-date=June 2, 2015}}{{failed verification|date=September 2020}}
• Cream (ex. Lanacane - active ingredient 3% Benzocaine)

Otic preparations:

• Solution (ex. Allergen)

Benzocaine is generally well tolerated and non-toxic when applied topically as recommended.Lexicomp Online, Adult and Pediatric Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2013; April 15, 2013.

However, there have been reports of serious, life-threatening adverse effects (e.g., seizures, coma, irregular heart beat, respiratory depression) with over-application of topical products or when applying topical products that contain high concentrations of benzocaine to the skin.{{cite web |author=U.S. Food and Drug Administration |title=FDA Public Health Advisory: Life-threatening side effects with use of skin products containing numbing ingredients for cosmetic procedures. |website=Food and Drug Administration |date=February 6, 2007 |archive-date=February 8, 2007 |archive-url=https://web.archive.org/web/20070208052946/http://www.fda.gov/cder/drug/advisory/topical_anesthetics.htm |access-date=June 13, 2024 |url=http://www.fda.gov/cder/drug/advisory/topical_anesthetics.htm |url-status=unfit}}

Overapplication of oral anesthetics such as benzocaine can increase the risk of pulmonary aspiration by relaxing the gag-reflex and allowing regurgitated stomach contents or oral secretions to enter the airway.{{medical citation needed|date=September 2020}} Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous.{{medical citation needed|date=September 2020}}

The topical use of higher concentration (10–20%) benzocaine products applied to the mouth or mucous membranes has been found to be a cause of methemoglobinemia, a disorder in which the amount of oxygen carried by the blood is greatly reduced.{{cite journal | vauthors = Shua-Haim JR, Gross JS | title = Methemoglobinemia toxicity from topical benzocaine spray | journal = Journal of the American Geriatrics Society | volume = 43 | issue = 5 | pages = 590 | date = May 1995 | pmid = 7730550 | doi = 10.1111/j.1532-5415.1995.tb06117.x | s2cid = 19563675 | doi-access = free }} This side effect is most common in children under two years of age.{{cite web |url=https://www.drugs.com/fda/benzocaine-topical-products-gels-liquids-risk-methemoglobinemia-12941.html |title=Benzocaine Topical Products: Sprays, Gels and Liquids – Risk of Methemoglobinemia |publisher=Drugs.com |access-date=March 20, 2014}} As a result, the FDA has stated that benzocaine products should not be used in children under two years of age, unless directed by and supervised by a healthcare professional.{{cite web|url=https://www.fda.gov/drugs/drugsafety/ucm250024.htm#safety |archive-url=https://web.archive.org/web/20110410232049/http://www.fda.gov/Drugs/DrugSafety/ucm250024.htm#safety |url-status=dead |archive-date=April 10, 2011 |title=FDA Drug Safety Communication: Reports of a rare, but serious and potentially fatal adverse effect with the use of over-the-counter (OTC) benzocaine gels and liquids applied to the gums or mouth |publisher=Fda.gov |access-date=June 2, 2015}} In European countries, the contraindication applies to children under 12 years of age. Symptoms of methemoglobinemia usually occur within minutes to hours of applying benzocaine, and can occur upon the first-time use or after additional use.

Benzocaine may cause allergic reactions.{{cite web|url=http://www.bedfordhospital.nhs.uk/upload_folder/patient%20information/allergy%20to%20benzocaine.pdf|title=Allergy to Benzocaine|access-date=March 20, 2014|url-status=dead|archive-url=https://web.archive.org/web/20140320095658/http://www.bedfordhospital.nhs.uk/upload_folder/patient%20information/allergy%20to%20benzocaine.pdf|archive-date=March 20, 2014}}{{cite journal | vauthors = Sidhu SK, Shaw S, Wilkinson JD | title = A 10-year retrospective study on benzocaine allergy in the United Kingdom | journal = American Journal of Contact Dermatitis | volume = 10 | issue = 2 | pages = 57–61 | date = June 1999 | pmid = 10357712 | doi = 10.1016/s1046-199x(99)90000-3 }}{{cite journal | vauthors = González-Rodríguez AJ, Gutiérrez-Paredes EM, Revert Fernández Á, Jordá-Cuevas E | title = Allergic contact dermatitis to benzocaine: the importance of concomitant positive patch test results | journal = Actas Dermo-Sifiliograficas | volume = 104 | issue = 2 | pages = 156–158 | date = March 2013 | pmid = 22551703 | doi = 10.1016/j.ad.2011.07.023 | url = http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90193182&pident_usuario=0&pcontactid=&pident_revista=403&ty=87&accion=L&origen=cardio&web=http://www.revespcardiol.org&lan=en&fichero=403v104n02a90193182pdf001.pdf | access-date = March 20, 2014 | url-status = dead | archive-url = https://web.archive.org/web/20160303234050/http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90193182&pident_usuario=0&pcontactid=&pident_revista=403&ty=87&accion=L&origen=cardio&web=http%3A%2F%2Fwww.revespcardiol.org&lan=en&fichero=403v104n02a90193182pdf001.pdf | archive-date = March 3, 2016 }}{{cite news| vauthors = Goldman L |url= http://www.cnn.com/2008/HEALTH/02/05/healthmag.creams/index.html?iref=newssearch |title=Go easy on medicated lotions, creams, gels |publisher=CNN |date=February 5, 2008 |access-date=March 20, 2014}} These include:

• Contact dermatitis (redness and itchiness)Cetylite Industries. Cetacaine (benzocaine 14%, tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept.
• Anaphylaxis (rare)

Pain is caused by the stimulation of free nerve endings. When the nerve endings are stimulated, sodium enters the neuron, causing depolarization of the nerve and subsequent initiation of an action potential. The action potential is propagated down the nerve toward the central nervous system, which interprets this as pain. Benzocaine acts to inhibit the voltage-gated sodium channels (VGSCs) on the neuron membrane, stopping the propagation of the action potential.{{Citation needed|date=January 2023}}

Benzocaine is the ethyl ester of p-aminobenzoic acid (PABA). It can be prepared from PABA and ethanol{{cite journal | doi = 10.1021/ed100838a | title = Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course | year = 2012 | vauthors = Demare P, Regla I | journal = Journal of Chemical Education | volume = 89 | issue = 1 | page = 147| bibcode = 2012JChEd..89..147D }} by Fischer esterification or via the reduction of ethyl p-nitrobenzoate. Benzocaine is sparingly soluble in water; it is more soluble in dilute acids and very soluble in ethanol, chloroform, and ethyl ether. The melting point of benzocaine is 88–92 °C,{{Cite web |title= Benzocaine |url=https://pubchem.ncbi.nlm.nih.gov/compound/2337#section=Melting-Point |access-date=March 27, 2023 | work = PubChem | publisher = U.S. National Library of Medicine |language=en}} and the boiling point is about 310 °C.{{cite book | title = D'Ans-Lax, Taschenbuch für Chemiker und Physiker | series =Organische Verbindungen |date=1983 |publisher=Springer Verlag |location=Berlin |isbn=3-540-12263-X |edition=4th}} The density of benzocaine is 1.17 g/cm³.

Benzocaine is commonly found, particularly in Britain, as an additive in street cocaine and also as a bulking agent in "legal highs".{{cite news|url=https://www.bbc.com/news/uk-10909884|title=Drug war targets cutting agents|work=BBC News |date=August 9, 2010}} Benzocaine gives a numbing effect similar to cocaine and as a bulking and binding agent it can not be detected once mixed. It is the most popular cutting agent worldwide.{{cite news| url = http://www.economist.com/node/21560270?fsrc=scn/tw_ec/all_cut_up | title = Drug prices: All cut up : Cocaine is cheaper, but weaker | newspaper = The Economist | date = August 11, 2012}}

Treatment of benzocaine with hydrazine leads to aminostimil, a compound related to isoniazid.

Benzocaine can be prepared by esterification using 4-aminobenzoic acid and ethanol.{{Cite journal | doi = 10.1002/cber.189502802150| title = Ueber Esterbildung bei aromatischen Amidosäuren| journal = Berichte der Deutschen Chemischen Gesellschaft| volume = 28| issue = 2| pages = 1917–1923| year = 1895| vauthors = Salkowski H | url = https://zenodo.org/record/1425796}}{{Cite journal | doi = 10.1002/jlac.18651350202| title = Ueber das durch Einwirkung von Jodwasserstoff auf Mannit beziehungsweise auf Melampyrin (Dulcit) entstehende β Hexyljodür und einige seiner Derivate| journal = Annalen der Chemie und Pharmacie| volume = 135| issue = 2| pages = 129–151| year = 1865| vauthors = Erlenmeyer E, Wanklyn JA | url = https://zenodo.org/record/1427245}} It can also be prepared by reduction of ethyl 4-nitrobenzoate to the amine.{{Cite journal | doi = 10.1002/jlac.18983030303| title = Ueber die Verbindungen aus Benzoylchlorid oder Phtalylchlorid und den Estern der drei Oxybenzoësäuren| journal = Justus Liebig's Annalen der Chemie| volume = 303| issue = 3| pages = 274–289| year = 1898| vauthors = Limpricht H | url = https://zenodo.org/record/1427505}}{{OrgSynth | vauthors = Adams R, Cohen FL |year=1928 |title=Ethyl p-aminobenzoate |volume=8 |pages=66 |collvol=1 |collvolpages=240 |prep=CV1P0240}} In industrial practice, the reducing agent is usually iron and water in the presence of a little acid.{{Cite book | doi = 10.1016/S0099-5428(08)60164-1| title = Benzocaine | volume = 12| pages = 73–104| series = Analytical Profiles of Drug Substances| year = 1983| vauthors = Ali SL | publisher = Academic Press | isbn = 978-0-12-260812-4}}

Benzocaine was first synthesized in 1890 by the German chemist Eduard Ritsert (1859–1946),Biography of Eduard Ritsert (in German): [http://www.deutsche-biographie.de/sfz106040.html Deutsche Biographie: Ritsert, Eduard.] in the town of Eberbach{{cite web|url=http://www.ritsert.de/index.php?option=com_content&task=view&lang=en&id=13&Itemid=27|title=100 years of Dr. Ritsert|publisher=Dr. Ritsert Pharma|access-date=March 14, 2010|archive-url=https://web.archive.org/web/20170909185714/http://www.ritsert.de/index.php?option=com_content&task=view&lang=en&id=13&Itemid=27|archive-date=September 9, 2017|url-status=dead}} and introduced to the market in 1902 under the name "Anästhesin".{{cite book | vauthors = Auterhoff H | title = Lehrbuch der pharmazeutischen Chemie | location = Stuttgart, Germany | publisher = Wissenschaftliche Verlagsgesellschaft | date = 1968 }}{{cite journal | vauthors = Ritsert E | date = 1925 | title = Über den Werdegang des Anästhesins | trans-title = On the development of Anaesthetics | language = German | journal = Pharmazeutische Zeitung | volume = 60 | pages = 1006–1008 }} See also: {{cite journal | vauthors = Friedrich C, Klimonow M | url = http://www.pharmazeutische-zeitung.de/index.php?id=31537 | title = 150. Geburtstag: Eduard Ritsert und das Anaesthesin | archive-url = https://web.archive.org/web/20140320125425/http://www.pharmazeutische-zeitung.de/index.php?id=31537 | archive-date = March 20, 2014 | trans-title = 150th birthday: Eduard Ritsert and Anästhetsin [Benzocaine] | language = German | journal = Pharmazeutische Zeitung Online | date = December 2014 }} First published clinical study demonstrating the efficacy of benzocaine: {{cite journal | vauthors = von Noorden C | date = 1902 | title = Ueber para-Aminobenzoesäure-Ester als locales Anästhetikum | trans-title = On [an] ester of para-aminobenzoic acid as a local anaesthetic | language = German | journal = Klinische Wochenschrift | volume = 39 | pages = 373–375 }}

Bath solutions of benzocaine and its derivatives are commonly used to anesthetize amphibians for surgery.{{cite journal | vauthors = Guénette SA, Giroux MC, Vachon P | title = Pain perception and anaesthesia in research frogs | journal = Experimental Animals | volume = 62 | issue = 2 | pages = 87–92 | date = 2013 | pmid = 23615302 | doi = 10.1538/expanim.62.87 | doi-access = free }}{{cite web|title=Amphibian Anesthesia — Research at Penn State|url=http://www.research.psu.edu/arp/anesthesia/amphibian-anesthesia.html|website=PennState Animal Resource Program|publisher=The Pennsylvania State University|access-date=August 24, 2017|location=State College, U.S.|language=en|date=November 8, 2010}} Benzocaine-based anesthetics are potent and highly effective for both anesthesia and euthanasia in amphibians.{{cite journal | vauthors = Barros AL, Lima AP, Fachin-Espinar MT, Nunez CV | title = Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae) | journal = PLOS ONE | volume = 15 | issue = 12 | pages = e0243654 | date = 2020 | pmid = 33290419 | pmc = 7723253 | doi = 10.1371/journal.pone.0243654 | bibcode = 2020PLoSO..1543654B | doi-access = free }}

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Category:4-Aminophenyl compounds

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