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Identification
NameBupivacaine
Accession NumberDB00297  (APRD00247)
Typesmall molecule
Groupsapproved, investigational
Description

A widely used local anesthetic agent. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+-)-BupivacaineNot AvailableNot Available
1-Butyl-2',6'-pipecoloxylidideNot AvailableNot Available
1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamideNot AvailableNot Available
BupivacainaSpanishINN
BupivacainumLatinINN
CarbostesinNot AvailableNot Available
dl-1-Butyl-2',6'-pipecoloxylidideNot AvailableNot Available
DL-BupivacaineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Bupivacaine Hydrochloride
14252-80-3
Thumb
  • InChI Key: SIEYLFHKZGLBNX-UHFFFAOYNA-N
  • Monoisotopic Mass: 324.196841267
  • Average Mass: 324.889
DBSALT000202
Brand names
NameCompany
BupivanSun
CarbostesinAstraZeneca
EXPARELNot Available
MarcainAstraZeneca
MarcainaAstraZeneca
MarcaineCareStream Dental
SensorcaineAstra Zeneca
Sensorcaine-MPFAstra Zeneca
VivacaineSeptodont
Brand mixtures
Brand NameIngredients
Marcaine EBupivacaine Hydrochloride + Epinephrine Bitartrate
Sensorcaine ForteBupivacaine Hydrochloride + Epinephrine Bitartrate
Categories
CAS number2180-92-9
WeightAverage: 288.4277
Monoisotopic: 288.220163528
Chemical FormulaC18H28N2O
InChI KeyLEBVLXFERQHONN-UHFFFAOYSA-N
InChI
InChI=1S/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)
IUPAC Name
1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
SMILES
CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C
Mass Specshow(8.44 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
SubclassAmino Acids, Peptides, and Analogues
Direct parentAlpha Amino Acid Amides
Alternative parentsAnilides; Piperidinecarboxylic Acids; Toluenes; Secondary Carboxylic Acid Amides; Tertiary Amines; Enolates; Carboxylic Acids; Polyamines
Substituentsacetanilide; piperidinecarboxylic acid; toluene; piperidine; benzene; carboxamide group; secondary carboxylic acid amide; tertiary amine; polyamine; carboxylic acid; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the alpha amino acid amides. These are amide derivatives of alpha amino acids.
Pharmacology
IndicationFor the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
PharmacodynamicsBupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
Mechanism of actionLocal anesthetics such as bupivacaine block 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. Bupivacaine binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. The analgesic effects of Bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.
AbsorptionThe rate of systemic absorption of local anesthetics 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 solution.
Volume of distributionNot Available
Protein binding95%
Metabolism

Amide-type local anesthetics such as bupivacaine are metabolized primarily in the liver via conjugation with glucuronic acid. The major metabolite of bupivacaine is 2,6-pipecoloxylidine, which is mainly catalyzed via cytochrome P450 3A4.

SubstrateEnzymesProduct
Bupivacaine
Not Available
2,6-pipecoloxylidineDetails
Route of eliminationOnly 6% of bupivacaine is excreted unchanged in the urine.
Half life2.7 hours in adults and 8.1 hours in neonates
ClearanceNot Available
ToxicityThe mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Bupivacaine Action PathwayDrug actionSMP00393
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9814
Blood Brain Barrier + 0.936
Caco-2 permeable + 0.6669
P-glycoprotein substrate Substrate 0.8435
P-glycoprotein inhibitor I Inhibitor 0.8582
P-glycoprotein inhibitor II Non-inhibitor 0.7836
Renal organic cation transporter Non-inhibitor 0.6471
CYP450 2C9 substrate Non-substrate 0.7957
CYP450 2D6 substrate Substrate 0.8346
CYP450 3A4 substrate Substrate 0.7045
CYP450 1A2 substrate Inhibitor 0.6863
CYP450 2C9 substrate Non-inhibitor 0.9099
CYP450 2D6 substrate Inhibitor 0.8932
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.6205
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6066
Ames test Non AMES toxic 0.8462
Carcinogenicity Non-carcinogens 0.8859
Biodegradation Not ready biodegradable 0.9729
Rat acute toxicity 2.2574 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8283
hERG inhibition (predictor II) Inhibitor 0.7851
Pharmacoeconomics
Manufacturers
  • Hospira inc
  • International medicated systems ltd
  • App pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
LiquidInfiltration
SolutionEpidural
SolutionInfiltration
SolutionIntraspinal
Prices
Unit descriptionCostUnit
Bupivacaine hcl powder18.36USDg
Sensorcaine-dextr 0.75% amp2.36USDml
Marcaine spinal ampul0.93USDml
Bupivacaine 0.5% on-q pump0.63USDml
Bupivacaine hcl 0.5% on-q pump0.63USDml
Bupivacaine 0.25% on-q pump0.62USDml
Marcaine 0.25% vial0.26USDml
Bupivacaine hcl-ns 0.0625%0.25USDml
Bupivacaine-ns 0.1% on-q pump0.25USDml
Sensorcaine 0.25% vial0.2USDml
Bupivacaine hcl-ns 0.1%0.17USDml
Bupivacaine hcl-ns 0.2%0.15USDml
Bupivacaine 0.25% vial0.11USDml
Bupivacaine 0.25% ampul0.1USDml
Bupivacaine hcl-ns 0.125% bag0.1USDml
Bupivacaine hcl-ns 0.25%0.1USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point107-108 °CPhysProp
water solubility2400 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.41HANSCH,C ET AL. (1995)
pKa8.1Not Available
Predicted Properties
PropertyValueSource
water solubility9.77e-02 g/lALOGPS
logP3.31ALOGPS
logP4.52ChemAxon
logS-3.5ALOGPS
pKa (strongest acidic)13.62ChemAxon
pKa (strongest basic)8ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area32.34ChemAxon
rotatable bond count5ChemAxon
refractivity90.19ChemAxon
polarizability34.19ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Thuresson, B. and Egner, B.P.H.; U.S. Patent 2,792,399; May 14, 1957; assigned to AB Bofors, Sweden.
Thuresson, B. and Pettersson, B.G.; US. Patent 2,955.1 11; October 4,1960; assigned to AB
Bofors, Sweden.

US2955111
General Reference
  1. Link
  2. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB: Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006 Jul;105(1):217-8. Pubmed
  3. Picard J, Meek T: Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006 Feb;61(2):107-9. Pubmed
External Links
ResourceLink
KEGG CompoundC07529
PubChem Compound2474
PubChem Substance46506768
ChemSpider2380
ChEBI3215
ChEMBLCHEMBL1098
Therapeutic Targets DatabaseDAP001229
PharmGKBPA135057240
IUPHAR2397
Guide to Pharmacology2397
Drug Product Database2165414
RxListhttp://www.rxlist.com/cgi/generic2/bupivacaine.htm
Drugs.comhttp://www.drugs.com/cdi/bupivacaine-solution.html
WikipediaBupivacaine
ATC CodesN01BB01N01BB10
AHFS Codes
  • 72:00.00
PDB EntriesNot Available
FDA labelshow(147 KB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
ConivaptanConivaptan may increase the serum concentration of CYP3A4 Substrates such as bupivacaine. Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates.
Food InteractionsNot Available

Targets

1. Sodium channel protein type 10 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 10 subunit alpha Q9Y5Y9 Details

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
  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
  3. Sheets MF, Fozzard HA, Lipkind GM, Hanck DA: Sodium channel molecular conformations and antiarrhythmic drug affinity. Trends Cardiovasc Med. 2010 Jan;20(1):16-21. Pubmed

2. Prostaglandin E2 receptor EP1 subtype

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Prostaglandin E2 receptor EP1 subtype P34995 Details

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
  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
  3. Beloeil H, Gentili M, Benhamou D, Mazoit JX: The effect of a peripheral block on inflammation-induced prostaglandin E2 and cyclooxygenase expression in rats. Anesth Analg. 2009 Sep;109(3):943-50. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Gantenbein M, Attolini L, Bruguerolle B, Villard PH, Puyoou F, Durand A, Lacarelle B, Hardwigsen J, Le-Treut YP: Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A. Drug Metab Dispos. 2000 Apr;28(4):383-5. Pubmed
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 02, 2014 10:14