Identification

Name
Chloroprocaine
Accession Number
DB01161  (APRD00404)
Type
Small Molecule
Groups
Approved
Description

Chloroprocaine hydrochloride is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine, like other local anesthetics, blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the action potential.

Structure
Thumb
Synonyms
  • 2-Chloroprocaine
  • 4-amino-2-Chlorobenzoic acid 2-(diethylamino)ethyl ester
  • Chloroprocain
  • Chloroprocaine
  • Chloroprocainum
  • Chlorprocaine
  • Cloroprocaina
Product Ingredients
IngredientUNIICASInChI Key
Chloroprocaine hydrochlorideLT7Z1YW11H3858-89-7SZKQYDBPUCZLRX-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ClorotekalInjection, solution10 mg/1mLIntrathecalB. Braun Medical Inc.2018-05-01Not applicableUs
ClorotekalInjection, solution10 mg/1mLIntrathecalSintetica Sa2017-10-042018-05-09Us
NesacaineInjection, solution10 mg/1mLInfiltration; PerineuralFresenius Kabi2010-10-14Not applicableUs
NesacaineInjection, solution20 mg/1mLInfiltration; PerineuralGeneral Injectables & Vaccines2013-01-30Not applicableUs
NesacaineInjection20 mg/1mLIntravenousAstra Zeneca Lp1996-10-012011-04-30Us
NesacaineInjection, solution20 mg/1mLInfiltration; PerineuralFresenius Kabi2010-10-14Not applicableUs
NesacaineInjection, solution10 mg/1mLInfiltration; PerineuralGeneral Injectables & Vaccines2011-10-03Not applicableUs
NesacaineInjection20 mg/1mLIntravenousAstra Zeneca Lp1990-09-302010-05-31Us
NesacaineInjection30 mg/1mLIntravenousAstra Zeneca Lp1996-10-012010-03-31Us
NesacaineInjection10 mg/1mLIntravenousAstra Zeneca Lp1990-09-302011-08-31Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Chloroprocaine HydrochlorideInjection, solution30 mg/1mLEpidural; Infiltration; IntracaudalHospira, Inc.2005-05-022013-07-01Us
Chloroprocaine HydrochlorideInjection, solution20 mg/1mLEpidural; InfiltrationBedford Pharmaceuticals1998-11-012012-06-30Us
Chloroprocaine HydrochlorideInjection, solution30 mg/1mLEpidural; Infiltration; Intracaudal; PerineuralWest-Ward Pharmaceuticals Corp1998-11-01Not applicableUs
Chloroprocaine HydrochlorideInjection, solution20 mg/1mLEpidural; Infiltration; IntracaudalHospira, Inc.2005-07-082013-01-01Us
Chloroprocaine HydrochlorideInjection, solution20 mg/1mLEpidural; Infiltration; Intracaudal; PerineuralWest-Ward Pharmaceuticals Corp1998-11-01Not applicableUs
Chloroprocaine HydrochlorideInjection, solution30 mg/1mLEpidural; InfiltrationBedford Pharmaceuticals1998-11-012012-06-30Us
International/Other Brands
Nesacaine-CE (AstraZeneca) / Piocaine
Categories
UNII
5YVB0POT2H
CAS number
133-16-4
Weight
Average: 270.755
Monoisotopic: 270.113505569
Chemical Formula
C13H19ClN2O2
InChI Key
VDANGULDQQJODZ-UHFFFAOYSA-N
InChI
InChI=1S/C13H19ClN2O2/c1-3-16(4-2)7-8-18-13(17)11-6-5-10(15)9-12(11)14/h5-6,9H,3-4,7-8,15H2,1-2H3
IUPAC Name
2-(diethylamino)ethyl 4-amino-2-chlorobenzoate
SMILES
CCN(CC)CCOC(=O)C1=C(Cl)C=C(N)C=C1

Pharmacology

Indication

For the production of local anesthesia by infiltration and peripheral nerve block. They are not to be used for lumbar or caudal epidural anesthesia.

Associated Therapies
Pharmacodynamics

Chloroprocaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Chloroprocaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Chloroprocaine is an ester anesthetic.

Mechanism of action

Chloroprocaine 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. It is hypothesized that Chloroprocaine binds or antagonizes the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

TargetActionsOrganism
ASodium channel protein type 10 subunit alpha
inhibitor
Human
UGlutamate receptor ionotropic, NMDA 3A
antagonist
Human
UNeuronal acetylcholine receptor subunit alpha-10
antagonist
Human
U5-hydroxytryptamine receptor 3A
antagonist
Human
USodium-dependent dopamine transporter
inhibitor
Human
Absorption

The rate of systemic absorption of local anesthetic drugs is dependent upon the total dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the anesthetic injection.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase.

Route of elimination

Chloroprocaine is rapidly metabolized in plasma by hydrolysis of the ester linkage by pseudocholinesterase. Urinary excretion is affected by urinary perfusion and factors affecting urinary pH.

Half life

21 +/- 2 seconds

Clearance
Not Available
Toxicity

In mice, the intravenous LD50 of chloroprocaine HCl is 97 mg/kg and the subcutaneous LD50 of chloroprocaine HCl is 950 mg/kg.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Chloroprocaine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Chloroprocaine can be decreased when used in combination with 1,10-Phenanthroline.
Aluminum sulfateThe therapeutic efficacy of Aluminum sulfate can be decreased when used in combination with Chloroprocaine.
AmbenoniumThe therapeutic efficacy of Chloroprocaine can be decreased when used in combination with Ambenonium.
Benzoic AcidThe therapeutic efficacy of Benzoic Acid can be decreased when used in combination with Chloroprocaine.
BisacodylThe therapeutic efficacy of Bisacodyl can be decreased when used in combination with Chloroprocaine.
BisoxatinThe therapeutic efficacy of Bisoxatin can be decreased when used in combination with Chloroprocaine.
Botulinum Toxin Type AThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Botulinum Toxin Type A.
Botulinum Toxin Type BThe risk or severity of adverse effects can be increased when Chloroprocaine is combined with Botulinum Toxin Type B.
Calcium polycarbophilThe therapeutic efficacy of Calcium polycarbophil can be decreased when used in combination with Chloroprocaine.
CarboxymethylcelluloseThe therapeutic efficacy of Carboxymethylcellulose can be decreased when used in combination with Chloroprocaine.
Food Interactions
Not Available

References

Synthesis Reference

Marks, H.C. and Rubin, M.I.; US. Patent 2,460,139; January 25,1949; assigned to Wallace & Tiernan Products, Inc.

General References
Not Available
External Links
Human Metabolome Database
HMDB0015292
KEGG Drug
D00732
KEGG Compound
C07877
PubChem Compound
8612
PubChem Substance
46508245
ChemSpider
8293
ChEBI
3636
ChEMBL
CHEMBL1179047
Therapeutic Targets Database
DAP000131
PharmGKB
PA448946
RxList
RxList Drug Page
Wikipedia
Chloroprocaine
ATC Codes
N01BA04 — Chloroprocaine
FDA label
Download (182 KB)
MSDS
Download (51.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentSurgical Anesthesia, Cesarean Section1
2CompletedNot AvailableShort Duration Lower Limb Surgery Via Spinal Anaesthesia1
2Not Yet RecruitingTreatmentDecrease Discharge Time Status Post Hemmoriodectomy / Return of Motor and Sensory Blockade / Spinal Anaesthesia1
2RecruitingTreatmentKnee Arthroscopy1
3Not Yet RecruitingTreatmentCesarean Section Complications / Pain NOS1
3RecruitingOtherAxillary nerve block therapy1
3RecruitingTreatmentUnplanned Caesarean Section1
4CompletedNot AvailableAnaesthesia therapy1
4CompletedTreatmentPain NOS1
4RecruitingOtherAdverse Reaction to Spinal Anesthetic / Maternal Care for Cervical Incompetence1
4RecruitingTreatmentCervical incompetence1
4Unknown StatusTreatmentPain Relief During Labour1
Not AvailableActive Not RecruitingPreventionArterial Hypotension1
Not AvailableCompletedNot AvailableAmbulatory Surgical Procedures / Inguinal Hernias / Spinal Anaesthesia / Umbilical Hernias1
Not AvailableCompletedNot AvailableAnaesthesia therapy / Neonates and Infants Who Have Received Chloroprocaine for Epidural Anesthesia1
Not AvailableCompletedNot AvailableImpact of Anesthetic Choice on Costs1
Not AvailableCompletedTreatmentSpinal Anaesthesia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • APP Pharmaceuticals
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Hospira Inc.
Dosage forms
FormRouteStrength
Injection, solutionEpidural; Infiltration20 mg/1mL
Injection, solutionEpidural; Infiltration30 mg/1mL
Injection, solutionEpidural; Infiltration; Intracaudal20 mg/1mL
Injection, solutionEpidural; Infiltration; Intracaudal30 mg/1mL
Injection, solutionIntrathecal10 mg/1mL
InjectionIntravenous10 mg/1mL
InjectionIntravenous20 mg/1mL
InjectionIntravenous30 mg/1mL
Injection, solutionInfiltration; Perineural10 mg/1mL
Injection, solutionInfiltration; Perineural20 mg/1mL
SolutionEpidural; Intracaudal20 mg
SolutionEpidural; Intracaudal30 mg
Injection, solutionEpidural; Infiltration; Intracaudal; Perineural20 mg/1mL
Injection, solutionEpidural; Infiltration; Intracaudal; Perineural30 mg/1mL
Prices
Unit descriptionCostUnit
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
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)173-174Marks, H.C. and Rubin, M.I.; US. Patent 2,460,139; January 25,1949; assigned to Wallace & Tiernan Products, Inc.
water solubility0.665 mg/mLNot Available
logP2.86HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility1.3 mg/mLALOGPS
logP2.72ALOGPS
logP2.48ChemAxon
logS-2.3ALOGPS
pKa (Strongest Basic)8.96ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.56 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity75.1 m3·mol-1ChemAxon
Polarizability28.74 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9772
Blood Brain Barrier+0.954
Caco-2 permeable+0.6107
P-glycoprotein substrateSubstrate0.5855
P-glycoprotein inhibitor INon-inhibitor0.8563
P-glycoprotein inhibitor IINon-inhibitor0.9707
Renal organic cation transporterNon-inhibitor0.6843
CYP450 2C9 substrateNon-substrate0.8593
CYP450 2D6 substrateNon-substrate0.6718
CYP450 3A4 substrateNon-substrate0.5215
CYP450 1A2 substrateInhibitor0.7507
CYP450 2C9 inhibitorNon-inhibitor0.8687
CYP450 2D6 inhibitorInhibitor0.7746
CYP450 2C19 inhibitorNon-inhibitor0.8061
CYP450 3A4 inhibitorNon-inhibitor0.8334
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6017
Ames testNon AMES toxic0.6613
CarcinogenicityNon-carcinogens0.6653
BiodegradationNot ready biodegradable0.9938
Rat acute toxicity2.7123 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8353
hERG inhibition (predictor II)Inhibitor0.5819
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-000i-9100000000-5a6841e384b0dfbd1238
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzoic acid esters. These are ester derivatives of benzoic acid.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoic acids and derivatives
Direct Parent
Benzoic acid esters
Alternative Parents
2-halobenzoic acids and derivatives / Aminobenzoic acids and derivatives / Aniline and substituted anilines / Benzoyl derivatives / Chlorobenzenes / Aryl chlorides / Vinylogous halides / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters
show 7 more
Substituents
Aminobenzoic acid or derivatives / Benzoate ester / 2-halobenzoic acid or derivatives / Halobenzoic acid or derivatives / Benzoyl / Aniline or substituted anilines / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide
show 19 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monochlorobenzenes, benzoate ester (CHEBI:3636)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity
Specific Function
Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference acro...
Gene Name
SCN10A
Uniprot ID
Q9Y5Y9
Uniprot Name
Sodium channel protein type 10 subunit alpha
Molecular Weight
220623.605 Da
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:17139284]
  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:17016423]
  3. Wong K, Strichartz GR, Raymond SA: On the mechanisms of potentiation of local anesthetics by bicarbonate buffer: drug structure-activity studies on isolated peripheral nerve. Anesth Analg. 1993 Jan;76(1):131-43. [PubMed:8418714]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein phosphatase 2a binding
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with reduced single-channel conductance, low calcium permeability and low voltage-dependent sensitivity to magnesium. Mediated by glycine. May ...
Gene Name
GRIN3A
Uniprot ID
Q8TCU5
Uniprot Name
Glutamate receptor ionotropic, NMDA 3A
Molecular Weight
125464.07 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor binding
Specific Function
Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an i...
Gene Name
CHRNA10
Uniprot ID
Q9GZZ6
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-10
Molecular Weight
49704.295 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Voltage-gated potassium channel activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Wilcox KM, Paul IA, Ordway GA, Woolverton WL: Role of the dopamine transporter and the sodium channel in the cocaine-like discriminative stimulus effects of local anesthetics in rats. Psychopharmacology (Berl). 2001 Sep;157(3):260-8. [PubMed:11605081]
  2. Mansbach RS, Jortani SA, Balster RL: Discriminative stimulus effects of esteratic local anesthetics in squirrel monkeys. Eur J Pharmacol. 1995 Feb 14;274(1-3):167-73. [PubMed:7768269]
  3. Wilcox KM, Paul IA, Woolverton WL: Comparison between dopamine transporter affinity and self-administration potency of local anesthetics in rhesus monkeys. Eur J Pharmacol. 1999 Feb 19;367(2-3):175-81. [PubMed:10078990]
  4. Wilcox KM, Rowlett JK, Paul IA, Ordway GA, Woolverton WL: On the relationship between the dopamine transporter and the reinforcing effects of local anesthetics in rhesus monkeys: practical and theoretical concerns. Psychopharmacology (Berl). 2000 Dec;153(1):139-47. [PubMed:11255924]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Kuhnert BR, Philipson EH, Pimental R, Kuhnert PM: A prolonged chloroprocaine epidural block in a postpartum patient with abnormal pseudocholinesterase. Anesthesiology. 1982 Jun;56(6):477-8. [PubMed:7081736]
  2. Tucker GT, Mather LE: Clinical pharmacokinetics of local anaesthetics. Clin Pharmacokinet. 1979 Jul-Aug;4(4):241-78. [PubMed:385208]
  3. Monedero P, Hess P: High epidural block with chloroprocaine in a parturient with low pseudocholinesterase activity. Can J Anaesth. 2001 Mar;48(3):318-9. [PubMed:11305839]
  4. Smith AR, Hur D, Resano F: Grand mal seizures after 2-chloroprocaine epidural anesthesia in a patient with plasma cholinesterase deficiency. Anesth Analg. 1987 Jul;66(7):677-8. [PubMed:3111302]
  5. Raj PP, Ohlweiler D, Hitt BA, Denson DD: Kinetics of local anesthetic esters and the effects of adjuvant drugs on 2-chloroprocaine hydrolysis. Anesthesiology. 1980 Oct;53(4):307-14. [PubMed:7425357]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:29