Procaine

Last updated
Procaine
Procaine.svg
Procaine-3D-xray.png
Clinical data
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU:B2
Routes of
administration
Parenteral
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
Pharmacokinetic data
Bioavailability N/A
Metabolism Hydrolysis by plasma esterases
Elimination half-life 40–84 seconds
Excretion Renal
Identifiers
  • 2-(diethylamino)ethyl 4-aminobenzoate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.388 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C13H20N2O2
Molar mass 236.315 g·mol−1
3D model (JSmol)
  • O=C(OCCN(CC)CC)c1ccc(N)cc1
  • 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 Yes check.svgY
  • Key:MFDFERRIHVXMIY-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth [1] and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of the trade name Novocain or Novocaine, in some regions, procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker. [2] Today, it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects. [3]

Contents

Procaine was first synthesized in 1905, [4] shortly after amylocaine. [5] It was created by the 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 a commonly used local anesthetic. [6] Einhorn wished his new discovery to be used for amputations, but for this surgeons preferred general anesthesia. Dentists, however, found it very useful. [7]

Pharmacology

Procaine application before removal of a decayed tooth US Navy 020623-M-7929S-040 Dental Officer participating in exercise Landing Force Cooperation Readiness and Training (LF CARAT).jpg
Procaine application before removal of a decayed tooth

The primary use for procaine is as an anaesthetic.

Aside from its use as a dental 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, thus is 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. [8] As a dental anesthesic, for example, more novocaine is needed for root canal treatment than for a simple filling. [1] 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.

A 1% procaine injection has been recommended for the treatment of extravasation complications associated with venipuncture, steroids, and 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. [9]

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.[ citation needed ] Studies on animals have shown the use of procaine led to the increase of dopamine and serotonin levels in the brain. [10] 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. [11]

Procaine can also cause allergic reactions causing 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. Allergic reactions are in fact quite rare, estimated to have an incidence of 1 per 500,000 injections. About one in 3000 white North Americans is homozygous (i.e. has two copies of the abnormal gene) for the most common atypical form of the enzyme pseudocholinesterase, [12] [13] and do not hydrolyze ester anesthetics such as procaine. This results in a prolonged period of high levels of the anesthetic in the blood and increased toxicity.

However, certain populations in the world such as the Vysya community in India commonly have a deficiency of this enzyme. [13]

Synthesis

Procaine can be synthesized in two ways.

Procaine synthesis Procaine synthesis.png
Procaine synthesis
  1. The first consists of the direct reaction of the 4-aminobenzoic acid ethyl ester with 2-diethylaminoethanol in the presence of sodium ethoxide.
  2. The second 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 to give Nitrocaine. Finally, the nitro group is reduced by hydrogenation over Raney nickel catalyst.

See also

Related Research Articles

Local anesthesia is any technique to induce the absence of sensation in a specific part of the body, generally for the aim of inducing local analgesia, i.e. local insensitivity to pain, although other local senses may be affected as well. It allows patients to undergo surgical and dental procedures with reduced pain and distress. In many situations, such as cesarean section, it is safer and therefore superior to general anesthesia.

<span class="mw-page-title-main">Local anesthetic</span> Medications to reversibly block pain

A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.

<span class="mw-page-title-main">Lidocaine</span> Local anesthetic

Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.

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 is a white solid, although commercial samples can appear gray. It is slightly soluble in water. It consists of a benzene ring substituted with amino and carboxyl groups. The compound occurs extensively in the natural world.

<span class="mw-page-title-main">Benzocaine</span> Local anaesthetic drug

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. In the European Union, the contraindication applies to children under 12 years of age.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

Pseudocholinesterase deficiency is an autosomal recessive inherited blood plasma enzyme abnormality in which the body's production of butyrylcholinesterase is impaired. People who have this abnormality may be sensitive to certain anesthetic drugs, including the muscle relaxants succinylcholine and mivacurium as well as other ester local anesthetics.

Infiltration analgesia is deposition of an analgesic (pain-relieving) drug close to the apex of a tooth so that it can diffuse to reach the nerve entering the apical foramina. It is the most routinely used in dental local treatment.

Benzonatate, sold under the brand name Tessalon among others, is a medication that is used for the symptomatic relief of cough. A 2023 systematic review found that there is inadequate evidence to support the effectiveness and safety of benzonatate for cough and highlighted rising safety concerns. Benzonatate is taken by mouth. Effects generally begin within 20 minutes and last 3 to 8 hours.

<span class="mw-page-title-main">Bupivacaine</span> Local anaesthetic drug

Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease sensation in a specific small area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of epinephrine to increase the duration of its action. It typically begins working within 15 minutes and lasts for 2 to 8 hours.

<span class="mw-page-title-main">Phentolamine</span> An α-adrenergic antagonist medication

Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α-adrenergic antagonist.

<span class="mw-page-title-main">Methohexital</span> Anesthetic and barbiturate-type sedative

Methohexital or methohexitone is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anesthetics.

<span class="mw-page-title-main">Chloroprocaine</span> Local anaesthetic drug

Chloroprocaine is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; this is in contrast to cocaine which vasoconstricts. Chloroprocaine is an ester anesthetic.

<span class="mw-page-title-main">Alfred Einhorn</span> German chemist (1856–1917)

Alfred Einhorn was a German chemist most notable for first synthesizing procaine in 1905 which he patented under the name Novocain. Until that time the primary anesthetic in use was cocaine, however its undesirable side effects led scientists to seek out newer anesthetic drugs. Novocain was found to be comparatively safe and effective, although its anesthetic effects were weaker than cocaine and some patients proved highly allergic. However, none of the other anesthetics developed during this period proved more effective and Novocain quickly became the standard local anesthesia. Although its use has largely been replaced by lidocaine, it is still in use today, most frequently in dentistry.

<span class="mw-page-title-main">Butyrylcholinesterase</span> Mammalian protein found in humans

Butyrylcholinesterase, also known asBChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it is made in the liver, found mainly in blood plasma, and encoded by the BCHE gene.

Dental anesthesia is the application of anesthesia to dentistry. It includes local anesthetics, sedation, and general anesthesia.

Amino esters are a class of local anesthetics. They are named for their ester bond and are unlike amide local anaesthetics.

<span class="mw-page-title-main">Dimethocaine</span> Stimulant

Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of the reward pathway in the brain. However, dimethocaine is a legal cocaine replacement in some countries and is even listed by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category “synthetic cocaine derivatives”. The structure of dimethocaine, being a 4-aminobenzoic acid ester, resembles that of procaine. It is found as a white powder at room temperature.

<span class="mw-page-title-main">Nitrobenzoic acid</span> Index of chemical compounds with the same name

Nitrobenzoic acids are derivatives of benzoic acid. Two are commercially important. They are about ten times more acidic than the parent benzoic acid.

References

  1. 1 2 "How long does numbness last after the dentist?". Medical News Today. May 22, 2018. Retrieved July 14, 2020.
  2. "Procaine (DB00721)". DrugBank. 2009-06-23.
  3. Hahn-Godeffroy JD (2011). "Procain-Reset: Ein Therapiekonzept zur Behandlung chronischer Erkrankungen" [Procaine reset: A therapy concept for the treatment of chronic diseases.]. Schweizerische Zeitschrift für Ganzheitsmedizin[ Swiss Journal of Integrative Medicine ] (in German). 23 (5): 291–6. doi: 10.1159/000332021 .
  4. Ritchie JM, Greene NM (1990). "Local Anesthetics" . In Gilman AG, Rall TW, Nies AS, Taylor P (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York: Pergamon Press. p.  311. ISBN   0-08-040296-8.
  5. Minard R (18 October 2006). "The Preparation of the Local Anesthetic, Benzocaine, by an Esterification Reaction" (PDF). Archived from the original (PDF) on 20 July 2011. Retrieved 10 March 2011. Adapted from Introduction to Organic Laboratory Techniques: A Microscale Approach, Pavia, Lampman, Kriz & Engel, 1989.
  6. Ruetsch YA, Böni T, Borgeat A (August 2001). "From cocaine to ropivacaine: the history of local anesthetic drugs". Current Topics in Medicinal Chemistry. 1 (3): 175–82. doi:10.2174/1568026013395335. PMID   11895133.
  7. Drucker P (May 1985). "The discipline of innovation". Harvard Business Review. 3 (3): 68. PMID   10272260.
  8. Sisk AL (1992). "Vasoconstrictors in local anesthesia for dentistry". Anesthesia Progress. 39 (6): 187–93. PMC   2148619 . PMID   8250339.
  9. "Procaine". ecstasydata.org.
  10. Sawaki K, Kawaguchi M (November 1989). "Some correlations between procaine-induced convulsions and monoamines in the spinal cord of rats". Japanese Journal of Pharmacology. 51 (3): 369–76. doi: 10.1254/jjp.51.369 . PMID   2622091.
  11. "Novocain Official FDA information". drugs.com. August 2007.
  12. Ombregt L (2013). "Procaine: Principles of Treatment". A System of Orthopaedic Medicine (3rd ed.). Churchill Livingstone. pp. 83–115. doi:10.1016/B978-0-7020-3145-8.00005-3. ISBN   978-0-7020-3145-8.
  13. 1 2 "Butyrylcholinesterase". OMIM. Retrieved 4 September 2015.
  14. Einhorn A, Fiedler K, Ladisch C, Uhlfelder E (1909). "Ueber p-Aminobenzoësäurealkaminester". Justus Liebig's Annalen der Chemie. 371 (2): 142–161. doi:10.1002/jlac.19093710204.
  15. Einhorn A Höchst Ag U.S. patent 812,554 ; DE 179627,"Verfahren zur Darstellung von p-Aminobenzoësäureaalkaminestern [Method for the prepareation of p-aminobenzoic acid alkamine esters]",published 1906-12-11, assigned to Höchst A.M. ; DE 194748,"Verfahren zur Darstellung von p-Aminobenzoësäureaalkaminestern [Method for the prepareation of p-aminobenzoic acid alkamine esters]",published 1908-01-28, assigned to Höchst A.M. , addendendum to DE 179627.

Further reading