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Benzocaine

Benzocaine, sold under the brand name Orajel amongst others, is a local anesthetic, belonging to the amino ester drug class, commonly used as a topical painkiller or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is combined with antipyrine to form A/B ear drops. In the US, products containing benzocaine for oral application are contraindicated in children younger than two years old.[2][3]

It was first synthesised in 1890 in Germany and approved for medical use in 1902.[4]

Medical uses

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

Examples of combination medications of benzocaine include:

  • Local anesthesia of oral and pharyngeal mucous membranes (sore throat, cold sores, mouth ulcers, toothache, sore gums, denture irritation)[5]
  • Otic pain (earache)[5]
  • Surgical or procedural local anesthesia[6]
  • Relief of skin pain caused by sunburn, ingrown toenails, hemorrhoids,[7]
  • Antipyrine-benzocaine otic consists of antipyrine and benzocaine, and is used to relieve ear pain and remove earwax.[8]
  • Cepacol consists of menthol and benzocaine, and is used to treat sore throat.[9]
  • A solution of benzocaine and menthol is marketed for the treatment of bee stings, mosquito bites, jellyfish stings, and other insect bites[10]

Other uses

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.[11][12]
  • Benzocaine mucoadhesive patches have been used in reducing orthodontic pain.[13]
  • 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[14] was once used there as pharmaceutical compound.

Available forms

Benzocaine can come in a variety of preparations including:

Oral preparations:

Topical preparations: Otic preparations:

  • Lozenges (ex. Cepacol, Mycinettes)[15]
  • Throat Spray (ex. Ultra Chloraseptic)[16]
  • Aerosol (ex. Topex)[17]
  • Gel (ex. Orajel, Kank-A)[18] [19]
  • Paste (ex. Orabase)[20]
  • Cream (ex. Lanacane - active ingredient 3% Benzocaine)
  • Solution (ex. Allergen)

Side effects

Benzocaine is generally well tolerated and non-toxic when applied topically as recommended.[21]

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.[22]

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.[23]

Benzocaine may cause allergic reactions.[24][25][26][27] These include:

  • Contact dermatitis (redness and itchiness)[28]
  • Anaphylaxis (rare)[28]

Chemistry

Benzocaine is the ethyl ester of p-aminobenzoic acid (PABA). It can be prepared from PABA and ethanol[29] 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,[30] and the boiling point is about 310 °C.[31] The density of benzocaine is 1.17 g/cm3.

Synthesis

Benzocaine can be prepared by esterification using 4-aminobenzoic acid and ethanol.[32][33] It can also be prepared by reduction of ethyl 4-nitrobenzoate to the amine.[34][35] In industrial practice, the reducing agent is usually iron and water in the presence of a little acid.[36]

History

Benzocaine was first synthesized in 1890 by the German chemist Eduard Ritsert (1859–1946),[37] in the town of Eberbach[38] and introduced to the market in 1902 under the name "Anästhesin".[39][40]

Society and culture

Benzocaine is found, particularly in Britain, as an additive in street cocaine and also as a bulking agent in "legal highs".[41] 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.[42]

Veterinary uses

Bath solutions of benzocaine and its derivatives are commonly used to anesthetize amphibians for surgery.[43][44] Benzocaine-based anesthetics are potent and highly effective for both anesthesia and euthanasia in amphibians.[45]

References

  1. Therapeutic Goods (Poisons Standard— June 2025) Instrument 2025 Therapeutic Goods Administration (TGA), May 2025, retrieved August 31, 2025^
  2. Safety Alerts for Human Medical Products - Oral Over-the-Counter Benzocaine Products: Drug Safety Communication - Risk of Serious and Potentially Fatal Blood Disorder U.S. Food and Drug Administration (FDA), retrieved May 26, 2018^
  3. Safety Information on Benzocaine-Containing Products U.S. Food and Drug Administration (FDA), June 25, 2018, retrieved December 1, 2025^
  4. Analogue-based Drug Discovery John Wiley & Sons, 2006^
  5. AHFS Drug Information 2007. McEvoy GK, ed. Benzocaine. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2844-5.^
  6. Sultan Healthcare. Topex metered spray (benzocaine 20%) prescribing information. Englewood, NJ; 2006.^
  7. Benzocaine topical^
  8. Antipyrine-Benzocaine Otic: MedlinePlus Drug Information medlineplus.gov, retrieved March 28, 2023^
  9. Cepacol Sore Throat (Benzocaine-Menthol) Mucous Membrane: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD www.webmd.com, retrieved March 28, 2023^
  10. STING-KILL - benzocaine and menthol solution^
  11. 'Longer-lasting' condom launched BBC News, June 17, 2002^
  12. Endurance Condoms The New York Times, December 15, 2002^
  13. The analgesic effect of benzocaine mucoadhesive patches on orthodontic pain caused by elastomeric separators, a preliminary study Acta Odontologica Scandinavica, September 2013^
  14. Produkty retrieved May 9, 2014^
  15. Cepacol Cepacol.com, retrieved June 2, 2015^
  16. Ultra Chloraseptic Anaesthetic Throat Spray 0.71% - Summary of Product Characteristics (SmPC) - (eMC) www.medicines.org.uk, retrieved May 5, 2018^
  17. Topex Metered Spray-Sultan Healthcare Sultanhc.com, retrieved June 2, 2015^
  18. Orajel - Oral Care for the Whole Family Orajel.com, May 11, 2015, retrieved June 2, 2015^
  19. Kank-A retrieved November 29, 2023^
  20. Colgate Orabase Paste with Benzocaine | Indications | Dental Products Colgateprofessional.com, retrieved June 2, 2015^
  21. Lexicomp Online, Adult and Pediatric Lexi-Drugs Online, Hudson, Ohio: Lexi-Comp, Inc.; 2013; April 15, 2013.^
  22. Risk of serious and potentially fatal blood disorder prompts FDA action on oral over-the-counter benzocaine products used for teething and mouth pain and prescription local anesthetics U.S. Food and Drug Administration (FDA), May 23, 2018, retrieved November 30, 2025^
  23. Methemoglobinemia toxicity from topical benzocaine spray Journal of the American Geriatrics Society, May 1995^
  24. Allergy to Benzocaine retrieved March 20, 2014^
  25. A 10-year retrospective study on benzocaine allergy in the United Kingdom American Journal of Contact Dermatitis, June 1999^
  26. Allergic contact dermatitis to benzocaine: the importance of concomitant positive patch test results Actas Dermo-Sifiliograficas, March 2013, retrieved March 20, 2014^
  27. Go easy on medicated lotions, creams, gels CNN, February 5, 2008, retrieved March 20, 2014^
  28. Cetylite Industries. Cetacaine (benzocaine 14%, tetracaine 2% and butamben 2%) spray, gel and liquid prescribing information. Pennsauken, NJ; 2006 Sept.^
  29. Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course Journal of Chemical Education, 2012^
  30. Benzocaine PubChem, U.S. National Library of Medicine, retrieved March 27, 2023^
  31. D'Ans-Lax, Taschenbuch für Chemiker und Physiker Springer Verlag, 1983^
  32. Ueber Esterbildung bei aromatischen Amidosäuren Berichte der Deutschen Chemischen Gesellschaft, 1895^
  33. Ueber das durch Einwirkung von Jodwasserstoff auf Mannit beziehungsweise auf Melampyrin (Dulcit) entstehende β Hexyljodür und einige seiner Derivate Annalen der Chemie und Pharmacie, 1865^
  34. Ueber die Verbindungen aus Benzoylchlorid oder Phtalylchlorid und den Estern der drei Oxybenzoësäuren Justus Liebig's Annalen der Chemie, 1898^
  35. {{OrgSynth | vauthors = Adams R, Cohen FL |year=1928 |title=Ethyl ''p''-aminobenzoate |volume=8 |pages=66 |collvol=1 |collvolpages=240 |prep=CV1P0240}}^
  36. Benzocaine Academic Press, 1983^
  37. Biography of Eduard Ritsert (in German): Deutsche Biographie: Ritsert, Eduard.^
  38. 100 years of Dr. Ritsert Dr. Ritsert Pharma, retrieved March 14, 2010^
  39. Lehrbuch der pharmazeutischen Chemie Wissenschaftliche Verlagsgesellschaft, 1968^
  40. See also: First published clinical study demonstrating the efficacy of benzocaine: Über den Werdegang des Anästhesins Pharmazeutische Zeitung, 1925 150. Geburtstag: Eduard Ritsert und das Anaesthesin Pharmazeutische Zeitung Online, December 2014 Ueber para-Aminobenzoesäure-Ester als locales Anästhetikum Klinische Wochenschrift, 1902^
  41. Drug war targets cutting agents BBC News, August 9, 2010^
  42. Drug prices: All cut up: Cocaine is cheaper, but weaker The Economist, August 11, 2012^
  43. Pain perception and anaesthesia in research frogs Experimental Animals, 2013^
  44. Amphibian Anesthesia — Research at Penn State PennState Animal Resource Program, The Pennsylvania State University, November 8, 2010, retrieved August 24, 2017^
  45. Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae) PLOS ONE, 2020^