Procaine

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Structural formula
Structural formula of procaine
General
Non-proprietary name Procaine
other names
  • 4-aminobenzoic acid β-diethylaminoethyl ester
  • 4-aminobenzoic acid 2- ( N , N -diethylamino) ethyl ester
  • [(Diethylamino) ethyl] -4-aminobenzoate
Molecular formula C 13 H 20 N 2 O 2
External identifiers / databases
CAS number
EC number 200-426-9
ECHA InfoCard 100,000,388
PubChem 4914
ChemSpider 4745
DrugBank DB00721
Wikidata Q423741
Drug information
ATC code
Drug class

Local anesthetics

Mechanism of action

Blockade of voltage-dependent sodium channels

properties
Molar mass
  • 236.31 g · mol -1 (procaine)
  • 272.77 g · mol -1 (· procaine hydrochloride)
Melting point
pK s value

8.05 (15 ° C)

solubility

Water: 9.45 g l −1 (30 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances

Hydrochloride

06 - Toxic or very toxic

danger

H and P phrases H: 301-317
P: 280-301 + 310
Toxicological data

350 mg kg −1 ( LD 50 ,  mouse ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Procaine is a local anesthetic of the ester type that was first used in dentistry. It is mainly known by the brand name Novocaine or Novocaine .

history

Procaine was synthesized and patented in 1904 by the German chemists Alfred Einhorn and Emil Uhlfelder and brought onto the market in 1905. The trade name for the product became Novocain (from the Latin novus “new” and -cain derived from cocaine ).

application

Before the discovery of procaine, cocaine was the most widely used local anesthetic. Procaine does not have a euphoric effect like cocaine and therefore does not fall under the scope of the narcotics laws and regulations. Today, procaine is rarely used for local anesthesia , as more effective substances that can penetrate far deeper, such as lidocaine , are available. Allergic and toxic reactions of the nervous system can occur in patients with Melkersson-Rosenthal syndrome .

Because of its low parasympatholytic , anti-inflammatory and perfusion-increasing effects, procaine is used in neural therapy , a type of treatment from alternative medicine .

Procaine can inhibit the enzyme DNA methylase . This property could be used to reverse paragenetic damage to gene expression . This is of particular interest in the case of damage to so-called tumor suppressor genes such as p53 .

Mechanism of action

The use of procaine blocks voltage-dependent sodium channels and thus prevents the rapid influx of sodium (which is responsible for depolarization on the cell membrane of axons). This prevents the transmission of excitation. To a lesser extent, other ion channels such as. B. blocked potassium channels . In order for the local anesthetic to act on the ion channel , it must penetrate the cell in its unprotonated form and attack the sodium channel there in its protonated form. The use in inflammatory tissue is made more difficult because there the pH balance is shifted to the side of the protonated form and the charged molecule does not penetrate the cell membrane.

Dismantling

Procaine is metabolized in the blood and tissues by pseudocholinesterase into paraaminobenzoic acid (PABA) and diethylaminoethanol.

Manufacturing

There are two different methods for procaine synthesis described in the literature. The base-catalyzed transesterification of ethyl 4-aminobenzoate with 2-diethylaminoethanol directly yields procaine:

Synthesis of procaine.

Alternatively, procaine can be made from 4-nitrobenzoic acid. These 4-nitrobenzoic acid with is thionyl chloride in 4-nitrobenzoic acid chloride converted. It is then esterified with 2-diethylaminoethanol and the nitro group is reduced to the amino group with hydrogen / Raney nickel .

Individual evidence

  1. ↑ a b Mutschler, Geisslinger, Kroemer, Schäfer-Korting, Mutschler drug effects, 8th edition, 2001, ISBN 3-8047-1763-2 , p. 267 ff.
  2. ↑ a b The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, pp. 1333-1334, ISBN 978-0-911910-00-1 .
  3. ↑ a b c Entry on procaine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  4. ↑ a b Data sheet Procaine hydrochloride from Sigma-Aldrich , accessed on April 22, 2011 ( PDF ).
  5. ↑ DRP 170587: Presentation of anesthetizing alkamine esters of o-, m- and p-aminobenzoic acid, salicylic acid and aminocinnamic acid , Farbwerke vorm. Master Lucius & Brüning, A. Einhorn, E. Uhlfelder.
  6. ↑ S. Isomura, TZ Hoffman, P. Wirsching, KD Janda: Synthesis, properties, and reactivity of cocaine benzoylthio ester possessing the cocaine absolute configuration. In: Journal of the American Chemical Society. Volume 124, Number 14, April 2002, pp. 3661-3668, PMID 11929256 . doi : 10.1021 / ja012376y .
  7. ↑ On the history of Novocain ( Memento from March 5, 2016 in the Internet Archive ) Apothekerzeitung issue 13/14 (1950) p. 175.
  8. ↑ U. Glade: The History of Anesthesia ( Memento from May 18, 2015 in the Internet Archive ), University of Bremen.
  9. ^ A. Villar-Garea, MF Fraga, J. Espada, M. Esteller: Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. In: Cancer Research . Volume 63, Number 16, August 2003, pp. 4984-4989, PMID 12941824 .
  10. ^ Axel Kleemann , Jürgen Engel, Bernd Kutscher and Dietmar Reichert: Pharmaceutical Substances, 4th edition (2000), 2 volumes published by Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 ; online since 2003 with biannual additions and updates.

Trade names

Monopreparations

Geroaslan-H3 (A), Gerovital H 3 (A), Hewedolor (D), KH3 (A), Lophakomp-Procain (D), Novanaest (A), Pasconeural (D), various generics (D)

Combination preparations

Gero-H 3 -Aslan (D), Fortepen (A), Ginvapast (CH), NeyChon (D), NeyGero (D), NeyGeront (D), Otalgan (D, CH), Otosan (CH), Retarpen compositum ( A)