Procaine

"Allocaine" redirects here. It is not to be confused with Allococaine.
"Novocaine" redirects here. For other uses, see Novocaine (disambiguation).
Procaine
Clinical data
AHFS/Drugs.com Monograph
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
Routes of
administration		 Parenteral
ATC code N01BA02 (WHO) C05AD05 (WHO) S01HA05 (WHO)
Legal status
Legal status
  • AU: S4 (Prescription only)
Pharmacokinetic data
Bioavailability n/a
Metabolism Hydrolysis by plasma esterases
Biological half-life 40–84 seconds
Excretion Renal
Identifiers
CAS Number 59-46-1 YesY
PubChem (CID) 4914
IUPHAR/BPS 4291
DrugBank DB00721 N
ChemSpider 4745 YesY
UNII 4Z8Y51M438 YesY
KEGG D08422 YesY
ChEBI CHEBI:8430 N
ChEMBL CHEMBL569 YesY
NIAID ChemDB 019136
ECHA InfoCard 100.000.388
Chemical and physical data
Formula C13H20N2O2
Molar mass 236.31 g/mol
3D model (Jmol) Interactive image
 NYesY (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 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]

Procaine was first synthesized in 1905,[3] shortly after amylocaine.[4] 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.[5]

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.[6] 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, 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.[7]

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.[8] 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.[9]

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. About one in 3000 white North Americans is homozygotic (i.e. has two copies of the abnormal gene) for the most common atypical form of the enzyme pseudocholinesterase,[10] 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, populations in the world, such as the Vysya community in India, more commoly have a deficiency of this enzyme.[10]

Synthesis

Procaine can be synthesized in two ways. The first consists of the direct reaction of the 4-aminobenzoic acid ethyl ester with 2-diethylaminoethanol in the presence of sodium ethoxide. 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. Finally, the nitro group is reduced by hydrogenation over Raney nickel catalyst.

Procaine synthesis[11][12]


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. 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. ↑ 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.
  6. ↑ Sisk AL. Vasoconstrictors in local anesthesia for dentistry. Anesth Prog. 1992;39:187–93.
  7. ↑ http://www.ecstasydata.org/search.php?substance1=2023
  8. ↑ 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.
  9. ↑ http://www.drugs.com/pro/novocain.html - Novocain Official FDA information. Updated(08/2007)
  10. 1 2 "BUTYRYLCHOLINESTERASE". OMIM. Retrieved 4 September 2015.
  11. ↑ 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.
  12. ↑ Alfred Einhorn, Höchst Ag U.S. Patent 812,554 DE 179627 DE 194748

Further reading

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