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

Similar Structures

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
N-(2-(diethylamino)ethyl)-2-butoxycinchoninamide
α-butyloxycinchonic acid-γ-diethylethylenediamine
α-butyloxycinchoninic acid diethylethylenediamide

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Cinchocaine hydrochloride	Z97702A5DG	61-12-1	IVHBBMHQKZBJEU-UHFFFAOYSA-N

Over the Counter Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
CVS Hemorrhoidal Topical Analgesic	Ointment	10 mg/1g	Topical	CVS Health	2014-01-17	Not applicable
Dibucaine	Cream	10 mg/1g	Topical	CVS Health	2010-07-16	Not applicable
Dibucaine	Ointment	0.28 g/28g	Topical	Geritrex Llc	2015-07-31	Not applicable
Dibucaine	Ointment	1 g/100g	Topical	Perrigo New York Inc.	2011-06-20	Not applicable
Dibucaine	Ointment	1 g/100g	Topical	E. Fougera & CO., A division of Fougera Pharmaceuticals Inc.	1968-01-01	Not applicable
Nupercainal	Ointment	1 g/100g	Topical	Dr. Reddy's Laboratories Inc.	2016-05-24	Not applicable
Nupercainal Anesthetic Ointment 1%	Ointment	1 %	Rectal; Topical	Glaxosmithkline Inc	1944-12-31	Not applicable

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Nupercainal Antiseptic Cream	Cinchocaine (0.5 %) + Domiphen bromide (0.05 %)	Cream	Topical	Glaxosmithkline Inc	1967-12-31	Not applicable
Proctol Ointment	Cinchocaine hydrochloride (0.5 %) + Esculin (1 %) + Framycetin sulfate (1 %) + Hydrocortisone (0.5 %)	Ointment	Rectal	Odan Laboratories Ltd	2003-08-06	Not applicable
Proctol Suppositories	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Suppository	Rectal	Odan Laboratories Ltd	2004-03-15	Not applicable
Proctosedyl Ointment	Cinchocaine hydrochloride (0.5 %) + Esculin (1 %) + Framycetin sulfate (1 %) + Hydrocortisone (0.5 %)	Ointment	Rectal	Aptalis Pharma Canada Ulc	2003-04-01	Not applicable
Proctosedyl Ointment	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Ointment	Rectal	Roussel Canada Inc.	1959-12-31	1997-08-05
Proctosedyl Ointment	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Ointment	Rectal	Hoechst Roussel Canada Inc.	1971-12-31	2006-07-28
Proctosedyl Sup	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Suppository	Rectal	Roussel Canada Inc.	1959-12-31	1996-09-09
Proctosedyl Suppositories	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Suppository	Rectal	Aptalis Pharma Canada Ulc	1997-01-23	Not applicable
Proctosedyl Suppositories	Cinchocaine hydrochloride (5 mg) + Esculin (10 mg) + Framycetin sulfate (10 mg) + Hydrocortisone (5 mg)	Suppository	Rectal	Hoechst Roussel Canada Inc.	1959-12-31	1999-08-11
Proctosone Ont	Cinchocaine hydrochloride (.5 %) + Esculin (1 %) + Hydrocortisone acetate (.5 %) + Neomycin sulfate (1 %)	Ointment	Rectal	Technilab Pharma Inc.	1981-12-31	2004-08-03

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.

Target	Actions	Organism
ASodium channel protein type 10 subunit alpha	inhibitor	Humans
ASodium channel protein type 5 subunit alpha	inhibitor	Humans
UCalmodulin	inhibitor	Humans

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

Pathway	Category
Dibucaine Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
Aclidinium	The therapeutic efficacy of Aclidinium can be decreased when used in combination with Cinchocaine.
Agmatine	The therapeutic efficacy of Agmatine can be decreased when used in combination with Cinchocaine.
Alcuronium	The therapeutic efficacy of Alcuronium can be decreased when used in combination with Cinchocaine.
Amitriptyline	The therapeutic efficacy of Amitriptyline can be decreased when used in combination with Cinchocaine.
Amobarbital	The therapeutic efficacy of Amobarbital can be decreased when used in combination with Cinchocaine.
Amoxapine	The therapeutic efficacy of Amoxapine can be decreased when used in combination with Cinchocaine.
Anisotropine methylbromide	The therapeutic efficacy of Anisotropine methylbromide can be decreased when used in combination with Cinchocaine.
Aprobarbital	The therapeutic efficacy of Aprobarbital can be decreased when used in combination with Cinchocaine.
Aripiprazole	The therapeutic efficacy of Aripiprazole can be decreased when used in combination with Cinchocaine.
Atracurium	The therapeutic efficacy of Atracurium can be decreased when used in combination with Cinchocaine.

Food Interactions

Not Available

References

Synthesis Reference

US1825623

General References

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]
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]
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

D04AB02 — Cinchocaine

S01HA06 — Cinchocaine

S02DA04 — Cinchocaine

N01BB06 — Cinchocaine

C05AD04 — Cinchocaine

AHFS Codes

84:08.00 — Antipruritics and Local Anesthetics

MSDS

Download (73.8 KB)

Clinical Trials

Clinical Trials: Not Available

Pharmacoeconomics

Manufacturers

Novartis pharmaceuticals corp

Packagers

Medisca Inc.
Novartis AG
Perrigo Co.

Dosage forms

Form	Route	Strength
Ointment	Topical	10 mg/1g
Cream	Topical	10 mg/1g
Ointment	Topical	0.28 g/28g
Ointment	Topical	1 g/100g
Ointment	Rectal; Topical	1 %
Cream	Topical
Ointment	Rectal
Suppository	Rectal
Kit

Prices

Unit description	Cost	Unit
Dibucaine hcl powder	4.74USD	g
Nupercainal 1% ointment	0.15USD	g
Dibucaine 1% ointment	0.12USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	99-101 °C (HCl salt)	Not Available
water solubility	42 mg/L (at 21 °C)	BEILSTEIN
logP	4.40	HANSCH,C ET AL. (1995)
logS	-3.7	ADME Research, USCD
pKa	8.85	SANGSTER (1994)

Predicted Properties

Property	Value	Source
Water Solubility	0.0389 mg/mL	ALOGPS
logP	3.79	ALOGPS
logP	3.7	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	14.57	ChemAxon
pKa (Strongest Basic)	9.04	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	54.46 Å²	ChemAxon
Rotatable Bond Count	10	ChemAxon
Refractivity	102.12 m³·mol^-1	ChemAxon
Polarizability	40.78 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9968
Blood Brain Barrier	+	0.9876
Caco-2 permeable	+	0.5187
P-glycoprotein substrate	Substrate	0.8702
P-glycoprotein inhibitor I	Inhibitor	0.7536
P-glycoprotein inhibitor II	Non-inhibitor	0.8862
Renal organic cation transporter	Non-inhibitor	0.6349
CYP450 2C9 substrate	Non-substrate	0.8297
CYP450 2D6 substrate	Non-substrate	0.6415
CYP450 3A4 substrate	Substrate	0.6842
CYP450 1A2 substrate	Inhibitor	0.9107
CYP450 2C9 inhibitor	Non-inhibitor	0.907
CYP450 2D6 inhibitor	Inhibitor	0.8932
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6424
Ames test	AMES toxic	0.6038
Carcinogenicity	Non-carcinogens	0.8128
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.6763 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.8924
hERG inhibition (predictor II)	Inhibitor	0.6851

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
GC-MS Spectrum - EI-B	GC-MS	splash10-000i-9000000000-11b0b035aed1c901a827
GC-MS Spectrum - CI-B	GC-MS	splash10-0006-5009000000-4623c33d494376e699f3
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0006-0009000000-396529f9f1539ca4f5d2
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-00di-0091000000-f6ba1af6a7e8fcdfaa16
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-00xr-0190000000-9cd7408320081da0e435
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-01b9-0960000000-48d5c97824dd28e11f73
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-cbd25496ff6fc8a2fa36
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014i-0900000000-b4f898603ef48a2b9e29
MS/MS Spectrum - , positive	LC-MS/MS	splash10-00xr-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

Details1. Sodium channel protein type 10 subunit alpha

Kind: Protein
Organism: Humans
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

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]
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]
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]
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]

Details2. Sodium channel protein type 5 subunit alpha

Kind: Protein
Organism: Humans
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

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]
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]
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]
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]
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]
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Details3. Calmodulin

Kind: Protein
Organism: Humans
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

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]
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]
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]
Sambandam T, Gunasekaran M: Purification and properties of calmodulin from Phymatotrichum omnivorum. Microbios. 1993;73(294):61-74. [PubMed:8382768]

Enzymes

Details1. Cholinesterase

Kind: Protein
Organism: Humans
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

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 April 21, 2019 05:23

Cinchocaine

Identification

Structure for Cinchocaine (DB00527)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References

References

References

Enzymes

References