Procaine
Encyclopedia
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 was 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
.
Procaine was first synthesized in 1905, shortly after amylocaine
, and is the oldest man-made local anesthetic still in clinical use for injection. 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 alkaloid
s used as anesthetics. It was introduced into medical use by surgeon Heinrich Braun
. Prior to the discovery of Stovaine
and Novocaine, cocaine
was the most commonly used local anesthetic.
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 often coadministered with epinephrine for the purpose of vasoconstriction. Vasoconstriction helps to reduce bleeding and prevents the drug from reaching systemic circulation in large amounts. Also unlike cocaine
, procaine does not have the euphoric
and addictive qualities that put it at risk for abuse. Cocaine is also not a vasodilator.
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 kidney
s into the urine
. Allergic reactions to procaine are usually not in response to procaine itself, but to PABA. About 1 in 3000 people have an atypical form of pseudocholinesterase, which does not hydrolyze ester anesthetics such as procaine, resulting in a prolonged period of high levels of the anesthetic in the blood and increased toxicity.
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.
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 (10mL of 1% procaine) as it helps relieve pain and vascular spasm.
Procaine is occasionally added as an additive in illicit street drugs such as cocaine
. It is also used by professional dominatrices
to enhance BDSM
play.
and serotonin
levels in the brain. Procaine can also cause allergic reactions causing the individuals to have problems with breathing, rashes, and swelling. Other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the excitation central nervous system which may lead to respiratory failure if overdosed. Procaine may also induce weakening of the myocardium leading to cardiac arrest
..
, the resulting acid chloride is then esterified with
2-diethylaminoethanol. Finally, the nitro group is reduced by hydrogenation over Raney nickel
catalyst.
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
drug of the amino ester
Amino esters
Amino esters are a class of local anesthetics.-Structure:Structurally, local anesthetics consist of three molecular components:* a lipophilic part* an intermediate aliphatic chain* a hydrophilic part...
group. It is used primarily to reduce the pain of intramuscular injection
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
, and it was also used in dentistry
Dentistry
Dentistry is the branch of medicine that is involved in the study, diagnosis, prevention, and treatment of diseases, disorders and conditions of the oral cavity, maxillofacial area and the adjacent and associated structures and their impact on the human body. Dentistry is widely considered...
. Owing to the ubiquity of the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Novocain, in some regions procaine is referred to generically as novocaine. It acts mainly by being a sodium channel blocker
Sodium channel blocker
Sodium channel blockers are agents that impair conduction of sodium ions through sodium channels.-Extracellular:The following naturally produced substances block sodium channels by binding to and occluding the extracellular pore opening of the channel:...
.
Procaine was first synthesized in 1905, shortly after amylocaine
Amylocaine
Amylocaine was the first synthetic local anesthetic. It was synthesized and patented under the name Stovaine by Ernest Fourneau at the Pasteur Institute in 1903. It was formerly used mostly in spinal anesthesia.-External links:...
, and is the oldest man-made local anesthetic still in clinical use for injection. It was created by the German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
chemist Alfred Einhorn who gave the chemical the trade name Novocaine, from the Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...
nov- (meaning new) and -caine, a common ending for alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s used as anesthetics. It was introduced into medical use by surgeon Heinrich Braun
Heinrich Braun
Heinrich Friedrich Wilhelm Braun was a German surgeon remembered for his work in the field of anaesthesiology. He was a native of Rawitsch, Province of Posen ....
. Prior to the discovery of Stovaine
Amylocaine
Amylocaine was the first synthetic local anesthetic. It was synthesized and patented under the name Stovaine by Ernest Fourneau at the Pasteur Institute in 1903. It was formerly used mostly in spinal anesthesia.-External links:...
and Novocaine, cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
was the most commonly used local anesthetic.
Procaine is used less frequently today since more effective (and hypoallergenic
Hypoallergenic
Hypoallergenic, meaning "below normal" or "slightly" allergenic, was a term first used in a cosmetics campaign in 1953. It is used to describe items that cause or are claimed to cause fewer allergic reactions...
) alternatives such as lidocaine
Lidocaine
Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
(Xylocaine) exist. Like other local anesthetics (such as mepivacaine
Mepivacaine
Mepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset and medium duration of action and is marketed under various trade names including Carbocaine and Polocaine.Mepivacaine became available in the United States in the 1960s.Mepivacaine is used in any...
, and prilocaine
Prilocaine
Prilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...
), procaine is a vasodilator, and is often coadministered with epinephrine for the purpose of vasoconstriction. Vasoconstriction helps to reduce bleeding and prevents the drug from reaching systemic circulation in large amounts. Also unlike cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, procaine does not have the euphoric
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
and addictive qualities that put it at risk for abuse. Cocaine is also not a vasodilator.
Procaine, an ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
anesthetic, is metabolized in the plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
by the enzyme pseudocholinesterase through hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
into para-amino benzoic acid (PABA), which is then excreted by the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s into the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
. Allergic reactions to procaine are usually not in response to procaine itself, but to PABA. About 1 in 3000 people have an atypical form of pseudocholinesterase, which does not hydrolyze ester anesthetics such as procaine, resulting in a prolonged period of high levels of the anesthetic in the blood and increased toxicity.
Procaine is the primary ingredient in the controversial preparation Gerovital H3 by Ana Aslan
Ana Aslan
Ana Aslan was a Romanian biologist and physician. She is considered to be a founding figure of gerontology and geriatrics in Romania. In 1952, under the leadership of Prof. Dr. Ana Aslan, the Geriatric Institute in Bucharest was founded...
(Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...
), 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.
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 (10mL of 1% procaine) as it helps relieve pain and vascular spasm.
Procaine is occasionally added as an additive in illicit street drugs such as cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
. It is also used by professional dominatrices
Dominatrix
Dominatrix or mistress is a woman or women who takes the dominant role in bondage, discipline and sadomasochism, or BDSM. A common form of address for a submissive to a dominatrix is "mistress", "ma'am", "domina" or "maîtresse"...
to enhance BDSM
BDSM
BDSM is an erotic preference and a form of sexual expression involving the consensual use of restraint, intense sensory stimulation, and fantasy power role-play. The compound acronym BDSM is derived from the terms bondage and discipline , dominance and submission , and sadism and masochism...
play.
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 that the use of procaine led to the increase of dopamineDopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
levels in the brain. Procaine can also cause allergic reactions causing the individuals to have problems with breathing, rashes, and swelling. Other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the excitation central nervous system which may lead to respiratory failure if overdosed. Procaine may also induce weakening of the myocardium leading to cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
..
Chemistry
Procaine, the 2-diethylaminoethyl ester of 4-aminobenzoic acid, is 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. The second way is by reacting 4-nitrobenzoic acid with thionyl chlorideThionyl chloride
Thionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
, the resulting acid chloride is then esterified with
2-diethylaminoethanol. Finally, the nitro group is reduced by hydrogenation over Raney nickel
Raney nickel
Raney nickel is a solid catalyst composed of fine grains of a nickel-aluminium alloy, used in many industrial processes. It was developed in 1926 by American]] engineer Murray Raney as an alternative catalyst for the hydrogenation of vegetable oils in industrial processes...
catalyst.
Further reading
- Hahn-Godeffroy, J.D.: 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, (1906).
- M. Lucius, (1904).
- M. Lucius, (1905).