Benzocaine

"Americaine" redirects here. For other uses, see Americain (disambiguation).

Benzocaine

Systematic (IUPAC) name
Ethyl 4-aminobenzoate
Clinical data
Trade names	Anbesol, Cepacol, Lanacane, Orajel
AHFS/Drugs.com	monograph
Pregnancy category	US: C (Risk not ruled out)
Legal status	UK: General sales list (GSL, OTC) US: OTC
Routes of administration	Topical
Identifiers
CAS Number	94-09-7 Y
ATC code	C05AD03 (WHO) D04AB04, QN01AX92 (WHO), N01BA05, R02AD01
PubChem	CID: 2337
DrugBank	DB01086 Y
ChemSpider	13854242 Y
UNII	U3RSY48JW5 Y
KEGG	D00552 Y
ChEBI	CHEBI:116735 Y
ChEMBL	CHEMBL278172 Y
Chemical data
Formula	C9H11NO2
Molecular mass	165.189 g/mol
SMILES O=C(OCC)c1ccc(N)cc1
InChI InChI=1S/C9H11NO2/c1-2-12-9(11)7-3-5-8(10)6-4-7/h3-6H,2,10H2,1H3 Y Key:BLFLLBZGZJTVJG-UHFFFAOYSA-N Y
(verify)

Benzocaine is a local anesthetic commonly used as a topical pain reliever or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is also combined with antipyrine to form A/B otic drops to relieve ear pain and remove earwax.

Chemical properties

Benzocaine is the ethyl ester of p-aminobenzoic acid (PABA). It can be prepared from PABA and ethanol 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 88–90 °C, and the boiling point is about 310 °C. The density of benzocaine is 1.17 g/cm³.

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".

Mechanism of action

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-dependent sodium channels (VDSCs) on the neuron membrane, stopping the propagation of the action potential.

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)
• Otic Pain (earache)
• Surgical or procedural local anesthesia

Formulations

Benzocaine can come in a variety of preparations including:
Oral preparations:

• Lozenges (ex. Cepacol, Mycinettes)

Topical preparations:

• Aerosol (ex. Topex)
• Gel (ex. Orajel)
• Paste (ex. Orabase)

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.

Over-application 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 (14-20%) benzocaine spray 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. This side effect is most common in children under 2 years of age. As a result, the FDA has stated that benzocaine products should not be used in children under 2 years of age, unless directed by and supervised by a healthcare professional. Symptoms of methemoglobinemia usually occur 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)
• Anaphylaxis (rare)

Other uses

Jiffy Toothache Drops bottle (7.75% Benzocaine)

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 swimmers 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.
• 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) used mainly after mosquito stings. Today's ready made Pudroderm was once used there as pharmaceutical compound.

Benzocaine is commonly found, particularly in Britain, as an impurity in street cocaine. Whilst giving a numbing effect similar to cocaine on users' gums it does not actually produce the effects of cocaine. Also benzocaine can and has been mistaken for a false positive for cocaine.

Synthesis

Prepd by the esterification of p-aminobenzoic acid: by the reduction of ethyl p-nitrobenzoate:

Benzocaine can be prepared by esterfication using 4-aminobenzoic acid and ethanol. It can also be prepared by reduction of ethyl 4-nitrobenzoate to the amine.

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

External links

• Public Health Advisory: Benzocaine Sprays by the Food and Drug Administration.