Identification

Name
Cinchocaine
Accession Number
DB00527  (APRD00915)
Type
Small Molecule
Groups
Approved, Vet approved
Description

A local anesthetic of the amide type now generally used for surface anesthesia. It is one of the most potent and toxic of the long-acting local anesthetics and its parenteral use is restricted to spinal anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1006)

Structure
Thumb
Synonyms
  • 2-butoxy-N-(2-(diethylamino)ethyl)cinchoninamide
  • 2-butoxy-N-(α-diethylaminoethyl)cinchoninamide
  • 2-butoxy-N-(β-diethylaminoethyl)cinchoninamide
  • 2-butoxy-N-[2-(diethylamino)ethyl]-4-quinolinecarboxamide
  • 2-Butoxy-quinoline-4-carboxylic acid (2-diethylamino-ethyl)-amide
  • 2-butoxyquinoline-4-carboxylic acid diethylaminoethylamide
  • 2-N-butoxy-N-(2-diethylaminoethyl)cinchoninamide
  • Cinchocaine
  • Cinchocainum
  • Cincocainio
  • Dibucaine
  • Dibucaine base
  • N-(2-(diethylamino)ethyl)-2-butoxycinchoninamide
  • α-butyloxycinchonic acid-γ-diethylethylenediamine
  • α-butyloxycinchoninic acid diethylethylenediamide
Product Ingredients
IngredientUNIICASInChI Key
Cinchocaine hydrochlorideZ97702A5DG61-12-1IVHBBMHQKZBJEU-UHFFFAOYSA-N
Dibucaine hydrochlorideNot AvailableNot AvailableNot applicable
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CVS Hemorrhoidal Topical AnalgesicOintment10 mg/1gTopicalCVS Health2014-01-17Not applicableUs
DibucaineOintment0.28 g/28gTopicalGeritrex Llc2015-07-31Not applicableUs
DibucaineOintment1 g/100gTopicalE. Fougera & CO., A division of Fougera Pharmaceuticals Inc.1968-01-01Not applicableUs
DibucaineCream10 mg/1gTopicalCVS Health2010-07-16Not applicableUs
DibucaineOintment1 g/100gTopicalPerrigo New York Inc.2011-06-20Not applicableUs
NupercainalOintment1 g/100gTopicalDr Reddy's Laboratories2016-05-24Not applicableUs
Nupercainal Anesthetic Ointment 1%Ointment1 %Rectal; TopicalGlaxosmithkline Inc1944-12-31Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Nupercainal Antiseptic CreamCinchocaine (0.5 %) + Domiphen bromide (0.05 %)CreamTopicalGlaxosmithkline Inc1967-12-31Not applicableCanada
Proctol OintmentDibucaine hydrochloride (0.5 %) + Esculin (1 %) + Framycetin sulfate (1 %) + Hydrocortisone (0.5 %)OintmentRectalOdan Laboratories Ltd2003-08-06Not applicableCanada
Proctol SuppositoriesDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)SuppositoryRectalOdan Laboratories Ltd2004-03-15Not applicableCanada
Proctosedyl OintmentDibucaine hydrochloride (0.5 %) + Esculin (1 %) + Framycetin sulfate (1 %) + Hydrocortisone (0.5 %)OintmentRectalAptalis Pharma Canada Ulc2003-04-01Not applicableCanada
Proctosedyl OintmentDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)OintmentRectalHoechst Roussel Canada Inc.1971-12-312006-07-28Canada
Proctosedyl OintmentDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)OintmentRectalRoussel Canada Inc.1959-12-311997-08-05Canada
Proctosedyl SupDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)SuppositoryRectalRoussel Canada Inc.1959-12-311996-09-09Canada
Proctosedyl SuppositoriesDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)SuppositoryRectalAptalis Pharma Canada Ulc1997-01-23Not applicableCanada
Proctosedyl SuppositoriesDibucaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)SuppositoryRectalHoechst Roussel Canada Inc.1959-12-311999-08-11Canada
Proctosone OntDibucaine hydrochloride (.5 %) + Esculin (1 %) + Hydrocortisone acetate (.5 %) + Neomycin sulfate (1 %)OintmentRectalTechnilab Pharma Inc.1981-12-312004-08-03Canada
International/Other Brands
Cincain / Nupercaine / Sovcaine
Categories
UNII
L6JW2TJG99
CAS number
85-79-0
Weight
Average: 343.4632
Monoisotopic: 343.225977187
Chemical Formula
C20H29N3O2
InChI Key
PUFQVTATUTYEAL-UHFFFAOYSA-N
InChI
InChI=1S/C20H29N3O2/c1-4-7-14-25-19-15-17(16-10-8-9-11-18(16)22-19)20(24)21-12-13-23(5-2)6-3/h8-11,15H,4-7,12-14H2,1-3H3,(H,21,24)
IUPAC Name
2-butoxy-N-[2-(diethylamino)ethyl]quinoline-4-carboxamide
SMILES
CCCCOC1=NC2=CC=CC=C2C(=C1)C(=O)NCCN(CC)CC

Pharmacology

Indication

For production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks.

Associated Conditions
Pharmacodynamics

Dibucaine is an amide-type local anesthetic, similar to lidocaine.

Mechanism of action

Local anesthetics block both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions through sodium channel inhibition. This reversibly stabilizes the membrane and inhibits depolarization, resulting in the failure of a propagated action potential and subsequent conduction blockade.

TargetActionsOrganism
ASodium channel protein type 10 subunit alpha
inhibitor
Human
ASodium channel protein type 5 subunit alpha
inhibitor
Human
UCalmodulin
inhibitor
Human
Absorption

In general, ionized forms (salts) of local anesthetics are not readily absorbed through intact skin. However, both nonionized (bases) and ionized forms of local anesthetics are readily absorbed through traumatized or abraded skin into the systemic circulation.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Primarily hepatic.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Subcutaneous LD50 in rat is 27 mg/kg. Symptoms of overdose include convulsions, hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest.

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

Interactions

Drug Interactions
DrugInteraction
AcebutololCinchocaine may increase the bradycardic activities of Acebutolol.
AcetylcholineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Acetylcholine.
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Cinchocaine.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Cinchocaine.
AlcuroniumThe therapeutic efficacy of Alcuronium can be decreased when used in combination with Cinchocaine.
AldosteroneThe therapeutic efficacy of Cinchocaine can be decreased when used in combination with Aldosterone.
AlprenololCinchocaine may increase the bradycardic activities of Alprenolol.
AmifampridineThe risk or severity of adverse effects can be increased when Cinchocaine is combined with Amifampridine.
AmitriptylineThe therapeutic efficacy of Amitriptyline can be decreased when used in combination with Cinchocaine.
AmobarbitalThe therapeutic efficacy of Amobarbital can be decreased when used in combination with Cinchocaine.
Food Interactions
Not Available

References

Synthesis Reference
US1825623
General References
  1. Abdel-Ghani NT, Youssef AF, Awady MA: Cinchocaine hydrochloride determination by atomic absorption spectrometry and spectrophotometry. Farmaco. 2005 May;60(5):419-24. [PubMed:15910814]
  2. Souto-Padron T, Lima AP, Ribeiro Rde O: Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi. Parasitol Res. 2006 Sep;99(4):317-20. Epub 2006 Apr 13. [PubMed:16612626]
  3. Nounou MM, El-Khordagui LK, Khalafallah N: Effect of various formulation variables on the encapsulation and stability of dibucaine base in multilamellar vesicles. Acta Pol Pharm. 2005 Sep-Oct;62(5):369-79. [PubMed:16459486]
External Links
Human Metabolome Database
HMDB0014668
KEGG Drug
D00733
KEGG Compound
C07879
PubChem Compound
3025
PubChem Substance
46506734
ChemSpider
2917
BindingDB
48532
ChEBI
247956
ChEMBL
CHEMBL1086
Therapeutic Targets Database
DAP000507
PharmGKB
PA449286
Drugs.com
Drugs.com Drug Page
Wikipedia
Dibucaine
ATC Codes
S02DA04 — CinchocaineN01BB06 — CinchocaineS01HA06 — CinchocaineC05AD04 — CinchocaineD04AB02 — Cinchocaine
AHFS Codes
  • 84:08.00 — Antipruritics and Local Anesthetics
MSDS
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Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Medisca Inc.
  • Novartis AG
  • Perrigo Co.
Dosage forms
FormRouteStrength
OintmentTopical10 mg/1g
CreamTopical10 mg/1g
OintmentTopical0.28 g/28g
OintmentTopical1 g/100g
OintmentRectal; Topical1 %
CreamTopical
OintmentRectal
SuppositoryRectal
Kit
Prices
Unit descriptionCostUnit
Dibucaine hcl powder4.74USD g
Nupercainal 1% ointment0.15USD g
Dibucaine 1% ointment0.12USD g
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)99-101 °C (HCl salt)Not Available
water solubility42 mg/L (at 21 °C)BEILSTEIN
logP4.40HANSCH,C ET AL. (1995)
logS-3.7ADME Research, USCD
pKa8.85SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0389 mg/mLALOGPS
logP3.79ALOGPS
logP3.7ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)14.57ChemAxon
pKa (Strongest Basic)9.04ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.46 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity102.12 m3·mol-1ChemAxon
Polarizability40.78 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9968
Blood Brain Barrier+0.9876
Caco-2 permeable+0.5187
P-glycoprotein substrateSubstrate0.8702
P-glycoprotein inhibitor IInhibitor0.7536
P-glycoprotein inhibitor IINon-inhibitor0.8862
Renal organic cation transporterNon-inhibitor0.6349
CYP450 2C9 substrateNon-substrate0.8297
CYP450 2D6 substrateNon-substrate0.6415
CYP450 3A4 substrateSubstrate0.6842
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6424
Ames testAMES toxic0.6038
CarcinogenicityNon-carcinogens0.8128
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6763 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8924
hERG inhibition (predictor II)Inhibitor0.6851
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
GC-MS Spectrum - EI-BGC-MSsplash10-000i-9000000000-11b0b035aed1c901a827
GC-MS Spectrum - CI-BGC-MSsplash10-0006-5009000000-4623c33d494376e699f3
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
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0006-0009000000-396529f9f1539ca4f5d2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00di-0091000000-f6ba1af6a7e8fcdfaa16
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00xr-0190000000-9cd7408320081da0e435
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-0960000000-48d5c97824dd28e11f73
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-cbd25496ff6fc8a2fa36
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-b4f898603ef48a2b9e29
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00xr-3980000000-e5e0b2d6136d950b770a

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinolones and derivatives. These are compounds containing a quinoline moiety which bears a ketone group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Quinolones and derivatives
Direct Parent
Quinolones and derivatives
Alternative Parents
Alkyl aryl ethers / Pyridines and derivatives / Benzenoids / Heteroaromatic compounds / Trialkylamines / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Quinolone / Alkyl aryl ether / Pyridine / Benzenoid / Heteroaromatic compound / Tertiary amine / Tertiary aliphatic amine / Carboximidic acid / Carboximidic acid derivative / Ether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, aromatic ether, monocarboxylic acid amide (CHEBI:247956)

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. Louro SR, Anteneodo C, Wajnberg E: Carboxyl groups at the membrane interface as molecular targets for local anesthetics. Biophys Chem. 1998 Aug 4;74(1):35-43. [PubMed:9742684]
  4. Ryan SE, Demers CN, Chew JP, Baenziger JE: Structural effects of neutral and anionic lipids on the nicotinic acetylcholine receptor. An infrared difference spectroscopy study. J Biol Chem. 1996 Oct 4;271(40):24590-7. [PubMed:8798723]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
Molecular Weight
226937.475 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. Oka M, Itoh Y, Fujita T: Halothane attenuates the cerebroprotective action of several Na+ and Ca2+ channel blockers via reversal of their ion channel blockade. Eur J Pharmacol. 2002 Oct 4;452(2):175-81. [PubMed:12354567]
  4. Louro SR, Anteneodo C, Wajnberg E: Carboxyl groups at the membrane interface as molecular targets for local anesthetics. Biophys Chem. 1998 Aug 4;74(1):35-43. [PubMed:9742684]
  5. Ryan SE, Demers CN, Chew JP, Baenziger JE: Structural effects of neutral and anionic lipids on the nicotinic acetylcholine receptor. An infrared difference spectroscopy study. J Biol Chem. 1996 Oct 4;271(40):24590-7. [PubMed:8798723]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Titin binding
Specific Function
Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins by Ca(2+). Among the enzymes to be stimulated by the calmodulin-Ca(2+) complex are a number...
Gene Name
CALM1
Uniprot ID
P0DP23
Uniprot Name
Calmodulin
Molecular Weight
16837.47 Da
References
  1. Muto Y, Kudo S, Nozawa Y: Effects of local anesthetics on calmodulin-dependent guanylate cyclase in the plasma membrane of Tetrahymena pyriformis. Biochem Pharmacol. 1983 Dec 1;32(23):3559-63. [PubMed:6140014]
  2. Volpi M, Sha'afi RI, Epstein PM, Andrenyak DM, Feinstein MB: Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin. Proc Natl Acad Sci U S A. 1981 Feb;78(2):795-9. [PubMed:6262771]
  3. Liu SH, Fu WM, Lin-Shiau SY: Studies on the inhibition by chlorpromazine of myotonia induced by ion channel modulators in mouse skeletal muscle. Eur J Pharmacol. 1993 Jan 26;231(1):23-30. [PubMed:7680317]
  4. Sambandam T, Gunasekaran M: Purification and properties of calmodulin from Phymatotrichum omnivorum. Microbios. 1993;73(294):61-74. [PubMed:8382768]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Elamin B: Dibucaine inhibition of serum cholinesterase. J Biochem Mol Biol. 2003 Mar 31;36(2):149-53. [PubMed:12689511]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 09:08