Procaine

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 as a sodium channel blocker.[1] Today it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects.[2]

"Allocaine" redirects here. It is not to be confused with Allococaine.
Procaine
Clinical data
AHFS/Drugs.comMonograph
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
    Routes of
    administration    		Parenteral
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    Pharmacokinetic data
    Bioavailabilityn/a
    MetabolismHydrolysis by plasma esterases
    Elimination half-life40–84 seconds
    ExcretionRenal
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    NIAID ChemDB
    CompTox Dashboard (EPA)
    ECHA InfoCard100.000.388
    Chemical and physical data
    FormulaC13H20N2O2
    Molar mass236.31 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    Procaine was first synthesized in 1905,[3] shortly after amylocaine.[4] 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.[5] Einhorn wished his new discovery to be used for amputations, but for this surgeons preferred general anesthesia. Dentists, however, found it very useful.[6]

    Pharmacology
    Procaine application before removal of a decayed tooth

    The primary use for procaine is as an 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, 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.[7] 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.[8]

    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.[9] 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.[10]

    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,[11][12] 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.[12]

    Synthesis

    Procaine can be synthesized in two ways.

    Procaine synthesis[13][14]
    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

    References
    1. DrugBank - Showing drug card for Procaine (DB00721) Update Date 2009-06-23
    2. J.D. Hahn-Godeffroy: Procain-Reset: Ein Therapiekonzept zur Behandlung chronischer Erkrankungen, Schweiz Z Ganzheitsmed 2011;23:291–296 (DOI:10.1159/000332021)
    3. Ritchie, J. Murdoch; Greene, Nicholas M. (1990). "Local Anesthetics". In Gilman, Alfred Goodman; Rall, Theodore W.; Nies, Alan S.; Taylor, Palmer (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York: Pergamon Press. p. 311. ISBN 0-08-040296-8.
    4. R. Minard, "The Preparation of the Local Anesthetic, Benzocaine, by an Esterification Reaction", Adapted from Introduction to Organic Laboratory Techniques: A Microscale Approach, Pavia, Lampman, Kriz & Engel, 1989. Revised 10/18/06
    5. Ruetsch, Y.A., Böni, T., and Borgeat, A. "From cocaine to ropivacaine: the history of local anesthetic drugs." Current Topics in Medical Chemistry, 1(3), 2001, p. 175-182.
    6. Drucker, P (May 1985). "The discipline of innovation". Harvard Business Review. 3: 68. The article was later reprinted in an August 2002 "best of Harvard Business Review" issue, and is viewable online at no cost.
    7. Sisk AL. Vasoconstrictors in local anesthesia for dentistry. Anesth Prog. 1992;39:187–93.
    8. ecstasydata.org
    9. Sawaki, K., and Kawaguchim, M. "Some Correlations between procaine-induced convulsions and monoamides in the spinal cord of rats". Japanese Journal of Pharmacology,51(3), 1989, p. 369-376.
    10. drugs.com, Novocain Official FDA information. Updated(08/2007)
    11. Ludwig Ombregt (2013). "Procaine: Principles of treatment". Science Direct.
    12. "BUTYRYLCHOLINESTERASE". OMIM. Retrieved 4 September 2015.
    13. Einhorn, A.; Fiedler, K.; Ladisch, C.; Uhlfelder, E. (1909). "Ueber p-Aminobenzoësäurealkaminester". Justus Liebig's Annalen der Chemie. 371 (2): 142. doi:10.1002/jlac.19093710204.
    14. Alfred Einhorn, Höchst Ag U.S. Patent 812,554 DE 179627 DE 194748

    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).
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