Procaine

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

"Allocaine" redirects here. It is not to be confused with Allococaine.

Procaine

Systematic (IUPAC) name
2-(diethylamino)ethyl 4-aminobenzoate
Clinical data
AHFS/Drugs.com	monograph
Pregnancy category	AU: B2 US: C (Risk not ruled out)
Legal status	AU: S4 (Prescription only)
Routes of administration	Parenteral
Pharmacokinetic data
Bioavailability	n/a
Metabolism	Hydrolysis by plasma esterases
Biological half-life	40–84 seconds
Excretion	Renal
Identifiers
CAS Number	59-46-1 Y
ATC code	N01BA02 (WHO) C05AD05 S01HA05
PubChem	CID: 4914
IUPHAR/BPS	4291
DrugBank	DB00721 N
ChemSpider	4745 Y
UNII	4Z8Y51M438 Y
KEGG	D08422 Y
ChEBI	CHEBI:8430 N
ChEMBL	CHEMBL569 Y
NIAID ChemDB	019136
Chemical data
Formula	C13H20N2O2
Molecular mass	236.31 g/mol
SMILES O=C(OCCN(CC)CC)c1ccc(N)cc1
InChI InChI=1S/C13H20N2O2/c1-3-15(4-2)9-10-17-13(16)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3 Y Key:MFDFERRIHVXMIY-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Procaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it is also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine. It acts mainly by being a sodium channel blocker. Today it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion enhancing, and mood enhancing effects.

Procaine was first synthesized in 1905, shortly after amylocaine. It was created by the German chemist Alfred Einhorn who gave the chemical the trade name Novocaine, from the Latin nov- (meaning new) and -caine, a common ending for alkaloids used as anesthetics. It was introduced into medical use by surgeon Heinrich Braun. Prior to the discovery of amylocaine and procaine, cocaine was the most commonly used local anesthetic. Einhorn wished his new discovery to be used for amputations, but surgeons preferred general anesthetic. Dentists, however, found it very useful. Einhorn was displeased by this perceived misuse of his "noble" invention and spent many years touring dental schools to advise them not to use it.

Pharmacology

Procaine application before removal of a decayed tooth

The primary use for procaine is as a topical anaesthetic.

Procaine is used less frequently today since more effective (and hypoallergenic) alternatives such as lidocaine (Xylocaine) exist. Like other local anesthetics (such as mepivacaine, and prilocaine), procaine is a vasodilator, and is thus often coadministered with epinephrine for the purpose of vasoconstriction. Vasoconstriction helps to reduce bleeding, increases the duration and quality of anesthesia, prevents the drug from reaching systemic circulation in large amounts, and overall reduces the amount of anesthetic required. Unlike cocaine, a vasoconstrictor, procaine does not have the euphoric and addictive qualities that put it at risk for abuse.

Procaine, an ester anesthetic, is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-amino benzoic acid (PABA), which is then excreted by the kidneys into the urine.

Procaine is the primary ingredient in the controversial preparation Gerovital H3 by Ana Aslan (Romania), which is claimed by its advocates to remedy many effects of aging. The mainstream medical view is that these claims were seriously studied and discredited in the 1960s.

A 1% procaine injection has been recommended for the treatment of extravasation complications associated with venipuncture (along with moist heat, ASA, steroids, antibiotics). It has likewise been recommended for treatment of inadvertent intra-arterial injections (10 ml of 1% procaine), as it helps relieve pain and vascular spasm.

Procaine is an occasional additive in illicit street drugs, such as cocaine. MDMA manufacturers also use procaine as an additive at ratios ranging from 1:1 up to 10% MDMA with 90% procaine, which can be life-threatening.

Adverse effects

Application of procaine leads to the depression of neuronal activity. The depression causes the nervous system to become hypersensitive producing restlessness and shaking, leading to minor to severe convulsions. Studies on animals have shown the use of procaine led to the increase of dopamine and serotonin levels in the brain. Other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the excitation of the central nervous system, which may lead to respiratory failure if overdosed. Procaine may also induce weakening of the myocardium leading to cardiac arrest.

Procaine can also cause allergic reactions causing the individuals to have problems with breathing, rashes, and swelling. Allergic reactions to procaine are usually not in response to procaine itself, but to its metabolite PABA. About one in 3000 white North Americans are homozygotic (i.e. they have two copies of the abnormal gene) for the commonest atypical form of the enzyme pseudocholinesterase, which means that they do not hydrolyze ester anesthetics such as procaine. The results in a prolonged period of high levels of the anesthetic in the blood and increased toxicity. However, there are populations in the world, such as the Vysya community in India, where deficiency of this enzyme is much more common.

Synthesis

Procaine can be synthesized in two ways. The first way consists of the direct reaction of the 4-aminobenzoic acid ethyl ester with 2-diethylaminoethanol in the presence of sodium ethoxide.

Procaine synthesis

The second way is by oxidizing 4-nitrotoluene to 4-nitrobenzoic acid, which is further reacted with thionyl chloride, the resulting acid chloride is then esterified with 2-diethylaminoethanol. Finally, the nitro group is reduced by hydrogenation over Raney nickel catalyst.

See also

• Procaine blockade
• Peter DeMarco
• Chloroprocaine

Further reading

• J.D. Hahn-Godeffroy: Wirkungen und Nebenwirkungen von Procain: was ist gesichert?. Komplement. integr. Med. 02/2007, 32-34.
• A. Einhorn, K. Fiedler, C. Ladish, E. Uhlfelder. Justus Liebigs Annalen der Chemie 371, 125, 131, 142, 162 (1910).
• A. Einhorn, M. Lucius, U.S. Patent 812,554 (1906).
• M. Lucius, DE 179627  (1904).
• M. Lucius, DE 194748  (1905).