PROCAINE DIHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H20N2O2.2H2O
Molecular Weight	272.3407
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O.O.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1

InChI

InChIKey=FOZXJARDUSNWJJ-UHFFFAOYSA-N

InChI=1S/C13H20N2O2.2H2O/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;2*1H2

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/monograph/procaine-hydrochloride.html | https://www.drugbank.ca/drugs/DB00721

Procaine 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. Procaine 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sodium channel alpha subunit 76 Target ID: CHEMBL2331043 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2167458 \| https://www.ncbi.nlm.nih.gov/pubmed/9768788 \| https://www.drugbank.ca/drugs/DB00721 \| http://www.genome.jp/dbget-bin/www_bget?dr:D00732 \| https://www.ncbi.nlm.nih.gov/pubmed/8981487	Blocker 537	60.0 nM [IC50]
Muscle-type nicotinic acetylcholine receptor 65 Target ID: CHEMBL2362997 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8531111	Antagonist 2778	50.0 µM [IC50]
Glutamate [NMDA] receptor subunit 3A 21 Target ID: CHEMBL4787 Sources: https://www.drugbank.ca/drugs/DB00721 \| https://www.ncbi.nlm.nih.gov/pubmed/16299047	Antagonist 2778
Serotonin 3a (5-HT3a) receptor 46 Target ID: CHEMBL2411 Sources: https://www.drugbank.ca/drugs/DB00721 \| https://www.ncbi.nlm.nih.gov/pubmed/7539114	Antagonist 2778	1.7 µM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.drugs.com/answers/what-are-the-indications-contraindictions-and-84645.html	Primary		Approved 8429	Procaine Approved Use Procaine is a local anesthetic. Procaine causes loss of feeling (numbness) of skin and mucous membranes. Procaine is used as an injection during surgery and other medical and dental procedures. Launch Date 1972

C_max

Value	Dose	Co-administered	Analyte	Population
12 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/573562/	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROCAINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
12.5 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/573562/	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROCAINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.3 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/573562/	60 mg/kg single, intravenous dose: 60 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		PROCAINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6362368 Page: p.304	healthy, 72.8 n = 119 Health Status: healthy Condition: Age-related decline Age Group: 72.8 Sex: M+F Population Size: 119 Sources: https://pubmed.ncbi.nlm.nih.gov/6362368 Page: p.304	Disc. AE: Systemic lupus erythematosus synd... AEs leading to discontinuation/dose reduction: Systemic lupus erythematosus synd (0.84%) Sources: https://pubmed.ncbi.nlm.nih.gov/6362368 Page: p.304

AEs

AE	Significance	Dose	Population
Systemic lupus erythematosus synd	0.84% Disc. AE	50 mg 1 times / day multiple, oral Studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6362368 Page: p.304	healthy, 72.8 n = 119 Health Status: healthy Condition: Age-related decline Age Group: 72.8 Sex: M+F Population Size: 119 Sources: https://pubmed.ncbi.nlm.nih.gov/6362368 Page: p.304

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.sciencedirect.com/science/article/pii/S1347861319302804

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8430	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8430
ChemicalBook	CB34796982	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB34796982
ChemicalBook	CB9296712	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9296712
ChemicalBook	CB94796979	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB94796979
MolPort	MolPort-000-889-177	https://www.molport.com/shop/molecule-link/MolPort-000-889-177
ZINC	ZINC000001530757	http://zinc15.docking.org/substances/ZINC000001530757
eMolecules	739616	https://www.emolecules.com/cgi-bin/more?vid=739616

PubMed

Title	Date	PubMed
The incidence of systemic side-effects following subconjunctival Mydricaine no. 1 injection.	1999 Dec	10707131
Minimal blocking concentrations of bupivacaine and procaine in an exclusively nociceptive system in humans.	1999 Jul-Aug	10445770
Spinal procaine with and without epinephrine and its relation to transient radicular irritation.	1999 Sep	10490152
Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.	2000 Feb	10728915
Changes in seizure susceptibility to local anesthetics by repeated administration of cocaine and nomifensine but not GBR12935: possible involvement of noradrenergic system.	2000 Jul	10952077
Pathways involved in RGD-mediated calcium transients in mature bovine oocytes.	2001	11945220
Swelling of capillary endothelial cells and cardiomyocytes in the ischaemic myocardium of artificially arrested canine hearts.	2001	11592680
Local anaesthetic effectivity and toxicity of fomocaine, five N-free fomocaine metabolites and two chiralic fomocaine derivatives in rats compared with procaine.	2001	11455675
[Potentiation of local anesthesia in endonasal surgery].	2001	11247245
Inhibition of the Na,K-ATPase of canine renal medulla by several local anesthetics.	2001 Apr	11352545
Supraventricular ectopics and supraventricular tachycardia following injection of subconjunctival Mydricaine No. 2.	2001 Aug	11767035
The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdaloid seizures in rats.	2001 Aug	11463518
[Rheologic infusion therapy, neurotransmitter administration and lidocaine injection in tinnitus. A staged therapeutic concept].	2001 Feb	11270201
Ionomycin and 2,5'-di(tertbutyl)-1,4,-benzohydroquinone elicit Ca2+-induced Ca2+ release from intracellular pools in Physarum polycephalum.	2001 Feb	11223389
Mechanical stress stimulates phospholipase C activity and intracellular calcium ion levels in neonatal rat cardiomyocytes.	2001 Feb	11162845
The effects of intracellular pH changes on resting cytosolic calcium in voltage-clamped snail neurones.	2001 Feb 1	11158272
The mechanism of maitotoxin-induced elevation of the cytosolic free calcium level in rat cerebrocortical synaptosomes.	2001 Jan	11243582
Establishment of a simple method for measurement of chronic blood flow in uterine artery of pregnant cows.	2001 Jul	11467811
Determination of apparent binding constants of drugs by capillary electrophoresis using beta-cyclodextrin as ligand and three different linear plotting methods.	2001 Jul 27	11521900
Subconjunctival anesthesia in contact diode laser cyclophotocoagulation.	2001 Jul-Aug	11475393
Clinical impact of histidine-ketoglutarate-tryptophan (HTK) cardioplegic solution on the perioperative period in open heart surgery patients.	2001 Jul-Aug	11440787
Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves.	2001 Jun	11442793
Retention behaviour and fluorimetric detection of procaine hydrochloride using carboxymethyl-beta-cyclodextrin as an additive in reversed-phase liquid chromatography.	2001 Jun 15	11442038
Interaction of local anaesthetic agents with the endogenous norepinephrine transporter in SH-SY5Y human neuroblastoma cells.	2001 Jun 15	11403930
Limbic responsiveness to procaine in cocaine-addicted subjects.	2001 Mar	11229979
Periorbital allergic contact dermatitis from oxybuprocaine.	2001 Mar	11218008
Limiting transient radicular irritation.	2001 Mar-Apr	11251145
Spinal anesthesia: a comparison of procaine and lidocaine.	2001 May	11394516
Intrathecal fentanyl-induced pruritus is more severe in combination with procaine than with lidocaine or bupivacaine.	2001 May-Jun	11359225
Release of non-neuronal acetylcholine from the isolated human placenta is mediated by organic cation transporters.	2001 Nov	11682442
Santayana's prophecy fulfilled.	2001 Nov-Dec	11707796
Oxybuprocaine induces a false-positive response in immunochromatographic SAS Adeno Test.	2002 Apr	11927446
Intrapericardial procaine affects volume expansion-induced fos immunoreactivity in unanesthetized rats.	2002 Apr	11922660
Activation of in vitro matured pig oocytes using activators of inositol triphosphate or ryanodine receptors.	2002 Apr 15	11943493
[Tumescent technique for local anesthesia].	2002 Feb	11865385
Improved right heart function after myocardial preservation with 2,3-butanedione 2-monoxime in a porcine model of allogenic heart transplantation.	2002 Jan	11782759
Non-surgical management of rectal tears in two mares.	2002 Mar	12019697

Patents

Sample Use Guides

In Vivo Use Guide

Adults Local or Regional Anesthesia Local Infiltration Usually, 350–600 mg, administered as diluted solution (i.e., 140–240 mL of a 0.25% solution or 70–120 mL of a 0.5% solution) Peripheral Nerve Block Up to 1 g, administered undiluted (i.e., 100 mL of a 1% injection) or as diluted solution (i.e., 200 mL of a 0.5% solution). For local infiltration or peripheral nerve block, inject slowly and avoid rapid injection of large volumes; when feasible, administer in fractional (incremental) doses. For subarachnoid (spinal) block, use 2-mL single-dose ampuls containing procaine hydrochloride 10% only.c d Position patient properly prior to spinal anesthesia.

Route of Administration: Other

In Vitro Use Guide

Procaine 0.2 mM reduced the maximal NMDA-induced currents without affecting the 50% effective concentration values for NMDA in mouse CA1 pyramidal neurons..

Name

Type

Language

PROCAINE DIHYDRATE

Common Name

English

PROCAINE, BASE DIHYDRATE

Common Name

English

PROCAINE DIHYDRATE [MI]

Common Name

English

BENZOIC ACID, P-AMINO-, 2-(DIETHYLAMINO)ETHYL ESTER, DIHYDRATE

Common Name

English

BENZOIC ACID, 4-AMINO-, 2-(DIETHYLAMINO)ETHYL ESTER, DIHYDRATE

Common Name

English

Code System Code Type Description

FDA UNII

ZNF8RW35GK