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Identification
NameProcaine
Accession NumberDB00721  (APRD00650)
TypeSmall Molecule
GroupsApproved, Investigational
Description

A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Diethylaminoethyl p-aminobenzoateNot AvailableNot Available
4-Aminobenzoic acid 2-diethylaminoethyl esterNot AvailableNot Available
beta-(Diethylamino)ethyl 4-aminobenzoateNot AvailableNot Available
beta-(Diethylamino)ethyl P-aminobenzoateNot AvailableNot Available
NovocaineNot AvailableNot Available
p-Aminobenzoic acid 2-diethylaminoethyl esterNot AvailableNot Available
ProcainaNot AvailableNot Available
ProcaineNot AvailableNot Available
ProcainumNot AvailableNot Available
Vitamin H3Not AvailableNot Available
β-(diethylamino)ethyl 4-aminobenzoateNot AvailableNot Available
β-(diethylamino)ethyl p-aminobenzoateNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
NovocainNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Procaine Hydrochloride
Thumb
  • InChI Key: HCBIBCJNVBAKAB-UHFFFAOYSA-N
  • Monoisotopic Mass: 272.129155633
  • Average Mass: 272.771
DBSALT000551
Categories
CAS number59-46-1
WeightAverage: 236.3101
Monoisotopic: 236.152477894
Chemical FormulaC13H20N2O2
InChI KeyMFDFERRIHVXMIY-UHFFFAOYSA-N
InChI
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
IUPAC Name
2-(diethylamino)ethyl 4-aminobenzoate
SMILES
CCN(CC)CCOC(=O)C1=CC=C(N)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentBenzoic acid esters
Alternative Parents
Substituents
  • Benzoate ester
  • Aminobenzoic acid or derivatives
  • Benzylether
  • Substituted aniline
  • Benzoyl
  • Aniline
  • Primary aromatic amine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed as a local anesthetic primarily in oral surgery
PharmacodynamicsProcaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine.
Mechanism of actionProcaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hydrolysis by plasma esterases to PABA

Route of eliminationWith normal kidney function, the drug is excreted rapidly by tubular excretion.
Half life7.7 minutes
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Procaine Action PathwayDrug actionSMP00402
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9747
Blood Brain Barrier+0.9533
Caco-2 permeable+0.6291
P-glycoprotein substrateSubstrate0.587
P-glycoprotein inhibitor INon-inhibitor0.9492
P-glycoprotein inhibitor IINon-inhibitor0.9884
Renal organic cation transporterNon-inhibitor0.684
CYP450 2C9 substrateNon-substrate0.8646
CYP450 2D6 substrateNon-substrate0.6643
CYP450 3A4 substrateNon-substrate0.6456
CYP450 1A2 substrateNon-inhibitor0.6308
CYP450 2C9 substrateNon-inhibitor0.9312
CYP450 2D6 substrateInhibitor0.8932
CYP450 2C19 substrateNon-inhibitor0.9294
CYP450 3A4 substrateNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7918
Ames testNon AMES toxic0.6165
CarcinogenicityNon-carcinogens0.6462
BiodegradationNot ready biodegradable0.9449
Rat acute toxicity2.5160 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8728
hERG inhibition (predictor II)Non-inhibitor0.6234
Pharmacoeconomics
Manufacturers
  • Eli lilly and co
  • Consolidated pharmaceutical group inc
  • King pharmaceuticals inc
  • Parke davis div warner lambert co
  • Pfizer laboratories div pfizer inc
  • Hospira inc
  • Abraxis pharmaceutical products
  • Bel mar laboratories inc
  • Elkins sinn div ah robins co inc
  • Gd searle llc
  • Miles laboratories inc
  • Watson laboratories inc
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Novocain 10% ampul2.4USD ml
Novocain 1% ampul1.79USD ml
Procaine hcl crystals1.76USD g
Nesacaine-mpf 3% vial1.34USD ml
Nesacaine-mpf 2% vial1.28USD ml
Nesacaine 2% vial0.74USD ml
Nesacaine 1% vial0.72USD ml
Chloroprocaine 3% vial0.33USD ml
Chloroprocaine 2% vial0.26USD ml
Procaine hcl 2% vial0.15USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point61 °CPhysProp
water solubility9450 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.14AVDEEF,A (1997)
logS-1.4ADME Research, USCD
pKa8.05 (at 15 °C)PERRIN,DD (1965)
Predicted Properties
PropertyValueSource
Water Solubility6.81 mg/mLALOGPS
logP2.1ALOGPS
logP1.88ChemAxon
logS-1.5ALOGPS
pKa (Strongest Basic)8.96ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.56 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity70.3 m3·mol-1ChemAxon
Polarizability26.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS1D NMR
References
Synthesis ReferenceUS812554
General Reference
  1. Gentry CL, Lukas RJ: Local anesthetics noncompetitively inhibit function of four distinct nicotinic acetylcholine receptor subtypes. J Pharmacol Exp Ther. 2001 Dec;299(3):1038-48. Pubmed
External Links
ATC CodesC05AD05N01BA02S01HA05
AHFS Codes
  • 24:04.04.04
  • 72:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.1 KB)
Interactions
Drug Interactions
Drug
AmiodaroneMay enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Amiodarone may increase the serum concentration of Antiarrhythmic Agents (Class Ia).
CimetidineMay decrease the excretion of Procainamide.
DarunavirMay increase the serum concentration of CYP2D6 Substrates.
FingolimodMay enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia).
LamotrigineMay increase the serum concentration of Procainamide.
LurasidoneMay enhance the QTc-prolonging effect of Procainamide.
MifepristoneMay enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents.
Peginterferon alfa-2bMay decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates.
PropafenoneMay enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia).
RanitidineMay increase the serum concentration of Procainamide. Ranitidine may also increase the concentration of the active N-acetyl-procainamide (NAPA) metabolite.
SulfadiazineMay diminish the therapeutic effect of Sulfonamide Derivatives.
SulfamethoxazoleMay diminish the therapeutic effect of Sulfonamide Derivatives.
SulfisoxazoleMay diminish the therapeutic effect of Sulfonamide Derivatives.
TrimethoprimMay increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide.
Food InteractionsNot Available

Targets

1. Sodium channel protein type 10 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 10 subunit alpha Q9Y5Y9 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Brau ME, Vogel W, Hempelmann G: Fundamental properties of local anesthetics: half-maximal blocking concentrations for tonic block of Na+ and K+ channels in peripheral nerve. Anesth Analg. 1998 Oct;87(4):885-9. Pubmed
  4. Katalymov LL: [The effect of inhibitors of sodium permeability (novocaine and tetrodotoxin) on the trace depolarization of myelinated nerve fibers] Fiziol Zh Im I M Sechenova. 1995 Sep;81(9):127-33. Pubmed
  5. Creveling CR, Bell ME, Burke TR Jr, Chang E, Lewandowski-Lovenberg GA, Kim CH, Rice KC, Daly JW: Procaine isothiocyanate: an irreversible inhibitor of the specific binding of [3H]batrachotoxinin-A benzoate to sodium channels. Neurochem Res. 1990 Apr;15(4):441-8. Pubmed

2. Glutamate receptor ionotropic, NMDA 3A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Glutamate receptor ionotropic, NMDA 3A Q8TCU5 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Hahnenkamp K, Durieux ME, Hahnenkamp A, Schauerte SK, Hoenemann CW, Vegh V, Theilmeier G, Hollmann MW: Local anaesthetics inhibit signalling of human NMDA receptors recombinantly expressed in Xenopus laevis oocytes: role of protein kinase C. Br J Anaesth. 2006 Jan;96(1):77-87. Epub 2005 Nov 18. Pubmed
  4. Nishizawa N, Shirasaki T, Nakao S, Matsuda H, Shingu K: The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons. Anesth Analg. 2002 Feb;94(2):325-30, table of contents. Pubmed

3. 5-hydroxytryptamine receptor 3A

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
5-hydroxytryptamine receptor 3A P46098 Details

References:

  1. Fan P, Weight FF: Procaine impairs the function of 5-HT3 receptor-ion channel complex in rat sensory ganglion neurons. Neuropharmacology. 1994 Dec;33(12):1573-9. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. Sodium-dependent dopamine transporter

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium-dependent dopamine transporter Q01959 Details

References:

  1. Sato T, Kitayama S, Mitsuhata C, Ikeda T, Morita K, Dohi T: Selective inhibition of monoamine neurotransmitter transporters by synthetic local anesthetics. Naunyn Schmiedebergs Arch Pharmacol. 2000 Feb;361(2):214-20. Pubmed
  2. Wilcox KM, Kimmel HL, Lindsey KP, Votaw JR, Goodman MM, Howell LL: In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys. Synapse. 2005 Dec 15;58(4):220-8. Pubmed
  3. Kiyatkin EA, Leon Brown P: The role of peripheral and central sodium channels in mediating brain temperature fluctuations induced by intravenous cocaine. Brain Res. 2006 Oct 30;1117(1):38-53. Epub 2006 Sep 7. Pubmed

5. Neuronal acetylcholine receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Neuronal acetylcholine receptor subunit alpha-2 Q15822 Details

References:

  1. Wang H, Zhang Y, Li ST: The effect of local anesthetics on the inhibition of adult muscle-type nicotinic acetylcholine receptors by nondepolarizing muscle relaxants. Eur J Pharmacol. 2010 Mar 25;630(1-3):29-33. Epub 2010 Jan 4. Pubmed

6. DNA

Kind: nucleotide

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details

References:

  1. Villar-Garea A, Fraga MF, Espada J, Esteller M: Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res. 2003 Aug 15;63(16):4984-9. Pubmed

7. Calcium-activated potassium channel

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Calcium-activated potassium channel subunit alpha-1 Q12791 Details
Calcium-activated potassium channel subunit beta-1 Q16558 Details
Calcium-activated potassium channel subunit beta-2 Q9Y691 Details
Calcium-activated potassium channel subunit beta-3 Q9NPA1 Details
Calcium-activated potassium channel subunit beta-4 Q86W47 Details
Intermediate conductance calcium-activated potassium channel protein 4 O15554 Details
Small conductance calcium-activated potassium channel protein 1 Q92952 Details
Small conductance calcium-activated potassium channel protein 2 Q9H2S1 Details
Small conductance calcium-activated potassium channel protein 3 Q9UGI6 Details

References:

  1. Benham CD, Bolton TB, Lang RJ, Takewaki T: The mechanism of action of Ba2+ and TEA on single Ca2+-activated K+ -channels in arterial and intestinal smooth muscle cell membranes. Pflugers Arch. 1985 Feb;403(2):120-7. Pubmed

8. Phospholipase A2

Kind: protein group

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details

References:

  1. Kunze H, Nahas N, Traynor JR, Wurl M: Effects of local anaesthetics on phospholipases. Biochim Biophys Acta. 1976 Jul 20;441(1):93-102. Pubmed

9. Lysophospholipase

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details

References:

  1. Kawashima Y, Nakagawa M, Suzuki Y, Uchiyama M: The relationship between chain elongation of palmitoyl-CoA and phospholipid content in rat liver microsomes. Biochim Biophys Acta. 1976 Aug 23;441(2):173-80. Pubmed

10. Monoamine oxidase

Kind: protein group

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Amine oxidase [flavin-containing] A P21397 Details
Amine oxidase [flavin-containing] B P27338 Details

References:

  1. MacFarlane MD: Procaine HCl (Gerovital H3): a weak, reversible, fully competitive inhibitor of monoamine oxidase. Fed Proc. 1975 Jan;34(1):108-10. Pubmed

Enzymes

1. Cholinesterase

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cholinesterase P06276 Details

References:

  1. Perez-Guillermo F, Delgado EM, Vidal CJ: Inhibition of human serum and rabbit muscle cholinesterase by local anesthetics. Biochem Pharmacol. 1987 Nov 1;36(21):3593-6. Pubmed
  2. Dorokhov KE, Grigorian GL: [Binding of reversible spin-labeled inhibitors with an butyrylcholinesterase active center]. Biofizika. 1986 Sep-Oct;31(5):746-51. Pubmed]

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Drug created on June 13, 2005 07:24 / Updated on February 03, 2015 14:12