PROCAINE BUTYRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H20N2O2.C4H8O2
Molecular Weight	324.4152
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=JJCJKGKSHRXGHT-UHFFFAOYSA-N

InChI=1S/C13H20N2O2.C4H8O2/c1-3-15(4-2)9-10-17-13(16)11-5-7-12(14)8-6-11;1-2-3-4(5)6/h5-8H,3-4,9-10,14H2,1-2H3;2-3H2,1H3,(H,5,6)

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
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
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
Calcification in the planula and polyp of the hydroid Hydractinia symbiolongicarpus (Cnidaria, Hydrozoa).	2001 Aug	11533115
The insular but not the perirhinal cortex is involved in the expression of fully-kindled amygdaloid seizures in rats.	2001 Aug	11463518
Local anesthetics noncompetitively inhibit function of four distinct nicotinic acetylcholine receptor subtypes.	2001 Dec	11714893
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
Penicillin concentrations in serum, milk, and urine following intramuscular and subcutaneous administration of increasing doses of procaine penicillin G in lactating dairy cows.	2001 Jul	11480523
Common solvent toxicity: autoxidation of respiratory redox-cyclers enforced by membrane derangement.	2001 Jul-Aug	11531077
[Hoigne syndrome as an acute non-allergic reaction to different drugs: case reports].	2001 Jun	11503262
Retention behaviour and fluorimetric detection of procaine hydrochloride using carboxymethyl-beta-cyclodextrin as an additive in reversed-phase liquid chromatography.	2001 Jun 15	11442038
High epidural block with chloroprocaine in a parturient with low pseudocholinesterase activity.	2001 Mar	11305839
Periorbital allergic contact dermatitis from oxybuprocaine.	2001 Mar	11218008
Spinal anesthesia: a comparison of procaine and lidocaine.	2001 May	11394516
Comparison of volatile anesthetic actions on intracellular calcium stores of vascular smooth muscle: investigation in isolated systemic resistance arteries.	2001 May	11388536
Bronchoconstrictive and relaxant effects of lidocaine on the airway in dogs.	2001 May	11378619
Changes in the flow properties of phospholipid dispersions induced by procaine hydrochloride. Effect of pH and temperature.	2001 May-Jul	11482791
Local anaesthetic activity of beta-caryophyllene.	2001 May-Jul	11482764
Neurotoxicity of spinal procaine--a caution.	2001 May-Jun	11359235
[Investigation on the mechanisms of leukocyte alteration in patients with intolerance to some drugs (with novocaine as a model)].	2001 Nov-Dec	11881499
[Interactions of histamine and glucocorticoids with nerve structures of respiration passages].	2001 Oct	11767456
[Infusion therapy with procaine in acute tinnitus].	2001 Oct	11699149
Optimisation and validation of a capillary electrophoresis method for the simultaneous determination of diazepam and otilonium bromide.	2001 Oct	11693609
[Treatment of animals with acute and/or chronic complaints by electric stimulation therapy].	2001 Oct 15	11699434
Role of the dopamine transporter and the sodium channel in the cocaine-like discriminative stimulus effects of local anesthetics in rats.	2001 Sep	11605081
Cembranoid and long-chain alkanol sites on the nicotinic acetylcholine receptor and their allosteric interaction.	2001 Sep 18	11551210
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
Clinical issues in the prophylaxis, diagnosis, and treatment of anthrax.	2002 Feb	11897081
Ionic basis of the resting membrane potential and action potential in the pharyngeal muscle of Caenorhabditis elegans.	2002 Feb	11826060
Chloroprocaine is less painful than lidocaine for skin infiltration anesthesia.	2002 Feb	11812697
The inhibition of the N-methyl-D-aspartate receptor channel by local anesthetics in mouse CA1 pyramidal neurons.	2002 Feb	11812692
Improved right heart function after myocardial preservation with 2,3-butanedione 2-monoxime in a porcine model of allogenic heart transplantation.	2002 Jan	11782759
Short-acting peribulbar anesthesia with 2-chloroprocaine.	2002 Jan	11777732
Allergy to local anaesthetics in dentistry. Myth or reality?	2002 Jan-Feb	11888487
Liver preservation with HTK: salutary effect of hypothermic aerobiosis by either gaseous oxygen or machine perfusion.	2002 Jun	12010145
Non-surgical management of rectal tears in two mares.	2002 Mar	12019697
Biochemical and morphological changes in pancreas stored under hypothermic conditions.	2002 Mar	12009654

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 BUTYRATE

Common Name

English

PROBUTYLIN

Brand Name

English

BUTANOIC ACID, COMPD. WITH 2-(DIETHYLAMINO)ETHYL 4-AMINOBENZOATE (1:1)

Common Name

English

PROCAINE BUTYRATE [MI]

Common Name

English

BENZOIC ACID, 4-AMINO-, BUTANOIC ACID, 2-(DIETHYLAMINO)ETHYL ESTER (1:1)

Common Name

English

P-AMINOBENZOIC ACID, 2-(DIETHYLAMINO)ETHYL ESTER BUTYRATE

Common Name

English

Code System Code Type Description

CAS

136-55-0