Benzocaine, sold under the brand name Orajel amongst others, is an

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...

local anesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general a ...

commonly used as a

topical A topical medication is a medication that is applied to a particular place on or in the body. Most often topical medication means application to body surfaces such as the skin or mucous membranes to treat ailments via a large range of classes ...

pain reliever Pain is a distressing feeling often caused by intense or damaging stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sensory and emotional experience associated with, or resembling that associated with, ...

or in cough drops. It is the active ingredient in many

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

anesthetic ointments such as products for

oral ulcer A mouth ulcer (aphtha) is an ulcer that occurs on the mucous membrane of the oral cavity. Mouth ulcers are very common, occurring in association with many diseases and by many different mechanisms, but usually there is no serious underlying caus ...

s. It is also combined with

antipyrine Phenazone (INN and BAN; also known as phenazon, antipyrine (USAN), or analgesine) is an analgesic (pain reducing), antipyretic (fever reducing) and anti-inflammatory drug. While it predates the term, it is often classified as a nonsteroidal anti ...

to form

A/B otic drops Antipyrine and benzocaine ear drops is a medication for the treatment of ear pain caused by otitis media. It combines antipyrine, an NSAID, and benzocaine, a numbing agent in order to treat ear pain, alongside hydroxyquinoline sulfate, an antisepti ...

to relieve

ear pain Ear pain, also known as earache or otalgia, is pain in the ear. Primary ear pain is pain that originates from the ear. Secondary ear pain is a type of referred pain, meaning that the source of the pain differs from the location where the pain is ...

and remove earwax. In the US, products containing benzocaine for oral application are contraindicated in children younger than two years old. In the European Union, the contraindication applies to children under 12 years of age. It was first synthesised in 1890 in Germany and approved for medical use in 1902.

Medical uses

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 anesthesia

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 Otitis media is a group of inflammatory diseases of the middle ear. One of the two main types is acute otitis media (AOM), an infection of rapid onset that usually presents with ear pain. In young children this may result in pulling at the ear, ...

'' and swimmers ear. * Some previous diet products such as

Ayds Ayds (pronounced as "aids") Reducing Plan Candy is a discontinued appetite-suppressant candy that enjoyed strong sales in the 1970s and early 1980s and was originally manufactured by The Carlay Company. Flavors Ayds was available in chocolat ...

. * Some condoms designed to prevent premature ejaculation. Benzocaine largely inhibits sensitivity on the

penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males d ...

, 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. * Benzocaine mucoadhesive patches have been used in reducing orthodontic pain. * In Poland it is included, together with menthol and zinc oxide, in the liquid powder (not to be confused with the liquid

face powder Face powder is a cosmetic product applied to the face to serve different functions, typically to beautify the face. Originating from ancient Egypt, face powder has had different social uses across cultures and in modern times, it is typically u ...

) used mainly after mosquito bites. Today's ready-made Pudroderm was once used there as pharmaceutical compound.

Available forms

Benzocaine can come in a variety of preparations including: Oral preparations: * Lozenges (ex. Cepacol, Mycinettes) * Throat Spray (ex. Ultra Chloraseptic) Topical preparations: * Aerosol (ex. Topex) * Gel (ex. Orajel) * Paste (ex. Orabase) * Cream (ex. Lanacane - active ingredient 3% Benzocaine) Otic preparations: * Solution (ex. Allergen)

Side effects

Benzocaine is generally well tolerated and non-toxic when applied topically as recommended. 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. 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. Applying an oral anesthetic and consuming beverages before going to bed can be particularly hazardous. 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 Methemoglobinemia, or methaemoglobinaemia, is a condition of elevated methemoglobin in the blood. Symptoms may include headache, dizziness, shortness of breath, nausea, poor muscle coordination, and blue-colored skin (cyanosis). Complications ...

, a disorder in which the amount of oxygen carried by the blood is greatly reduced. This side effect is most common in children under two years of age. 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. 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. 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 Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

(rare)

Pharmacology

Pharmacodynamics

Pain is caused by the stimulation of free nerve endings. When the

nerve ending A free nerve ending (FNE) or bare nerve ending, is an unspecialized, afferent nerve fiber sending its signal to a sensory neuron. ''Afferent'' in this case means bringing information from the body's periphery toward the brain. They function as cut ...

s are stimulated,

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

enters the

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa ...

, causing depolarization of the nerve and subsequent initiation of an

action potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells ...

. The action potential is propagated down the nerve toward the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

, which interprets this as pain. Benzocaine acts to inhibit the voltage-dependent sodium channels (VDSCs) on the

membrane, stopping the propagation of the action potential.

Chemistry

Benzocaine is the ethyl

of ''p''-aminobenzoic acid (PABA). It can be prepared from PABA and

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...

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 Chloroform, or trichloromethane, is an organic compound with formula C H Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various ...

, and ethyl ether. The

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depen ...

of benzocaine is 88–90 °C, and the

boiling point The boiling point of a substance is the temperature at which the vapor pressure of a liquid equals the pressure surrounding the liquid and the liquid changes into a vapor. The boiling point of a liquid varies depending upon the surrounding env ...

is about 310 °C. The

density Density (volumetric mass density or specific mass) is the substance's mass per unit of volume. The symbol most often used for density is ''ρ'' (the lower case Greek letter rho), although the Latin letter ''D'' can also be used. Mathematicall ...

of benzocaine is 1.17 g/cm³. Benzocaine is commonly found, particularly in Britain, as an additive in street

cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...

and also as a bulking agent in "legal highs". Whilst giving a numbing effect similar to cocaine, users prefer Benzocaine as it is a better bulking and binding agent that can't be detected once mixed. Benzocaine is the most popular cutting agent worldwide. Treatment of benzocaine with hydrazine leads to aminostimil, a compound related to isoniazid.

Synthesis

Benzocaine can be prepared by esterification using

4-aminobenzoic acid 4-Aminobenzoic acid (also known as ''para''-aminobenzoic acid or PABA because the two functional groups are attached to the benzene ring across from one another in the ''para'' position) is an organic compound with the formula H2NC6H4CO2H. PABA i ...

and

. It can also be prepared by reduction of ethyl 4-nitrobenzoate to the

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...

. In industrial practice, the reducing agent is usually iron and water in the presence of a little acid.

History

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

Veterinary medicine

A bath solution of benzocaine has been used to anesthetize amphibians for surgery.

References

External links

* {{Portal bar , Medicine 4-Aminobenzoate esters Ethyl esters Local anesthetics Sodium channel blockers Wyeth brands