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Identification
Name Bupivacaine
Accession Number DB00297 (APRD00247)
Type small molecule
Groups approved
Description

A widely used local anesthetic agent. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
(+-)-Bupivacaine
Bloqueina
Bupivacaina [INN-Spanish]
Bupivacaine HCL
Bupivacaine HCL KIT
Bupivacainum [INN-Latin]
cBupivacaine
DL-Bupivacaine
DUR-843
LAC-43
Salts Not Available
Brand names
Name Company
Anekain
Bupivan
Carbostesin
Marcaina
Marcaine
Marcaine HCL
Sensorcaine
Sensorcaine-MPF
Brand mixtures
Brand Name Ingredients
Marcaine E Bupivacaine Hydrochloride + Epinephrine Bitartrate
Sensorcaine Forte Bupivacaine Hydrochloride + Epinephrine Bitartrate
Categories
  • Anesthetics, Local
CAS number 2180-92-9
Weight Average: 288.4277
Monoisotopic: 288.220163528
Chemical Formula C18H28N2O
InChI Key InChIKey=LEBVLXFERQHONN-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)
Plain Text
IUPAC Name
1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
SMILES
CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C
Plain Text
Mass Spec show (8.44 KB)
Taxonomy
Kingdom Organic
Classes
  • Acetanilides
Substructures
  • Amino Ketones
  • Benzene and Derivatives
  • Acetanilides
  • Carboxylic Acids and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Anilines
  • Piperidines
Pharmacology
Indication For the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
Pharmacodynamics Bupivacaine 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 action Local 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.
Absorption The 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 distribution Not Available
Protein binding 95%
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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Bupivacaine
    		2,6-pipecoloxylidine Details
    Route of elimination Only 6% of bupivacaine is excreted unchanged in the urine.
    Half life 2.7 hours in adults and 8.1 hours in neonates
    Clearance Not Available
    Toxicity The 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
    Pathway Name SMPDB ID
    Smp00393 Bupivacaine Pathway SMP00393
    Pharmacoeconomics
    Manufacturers
    • Hospira inc
    • International medicated systems ltd
    • App pharmaceuticals llc
    Packagers
    Dosage forms
    Form Route Strength
    Liquid Infiltration
    Solution Epidural
    Solution Infiltration
    Solution Intraspinal
    Prices
    Unit description Cost Unit
    Bupivacaine hcl powder 18.36 USD g
    Sensorcaine-dextr 0.75% amp 2.36 USD ml
    Marcaine spinal ampul 0.93 USD ml
    Bupivacaine 0.5% on-q pump 0.63 USD ml
    Bupivacaine hcl 0.5% on-q pump 0.63 USD ml
    Bupivacaine 0.25% on-q pump 0.62 USD ml
    Marcaine 0.25% vial 0.26 USD ml
    Bupivacaine hcl-ns 0.0625% 0.25 USD ml
    Bupivacaine-ns 0.1% on-q pump 0.25 USD ml
    Sensorcaine 0.25% vial 0.2 USD ml
    Bupivacaine hcl-ns 0.1% 0.17 USD ml
    Bupivacaine hcl-ns 0.2% 0.15 USD ml
    Bupivacaine 0.25% vial 0.11 USD ml
    Bupivacaine 0.25% ampul 0.1 USD ml
    Bupivacaine hcl-ns 0.125% bag 0.1 USD ml
    Bupivacaine hcl-ns 0.25% 0.1 USD ml
    First Prev Next Last
    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 107-108 °C PhysProp
    water solubility 2400 mg/L (at 25 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP 3.41 HANSCH,C ET AL. (1995)
    pKa 8.1 Not Available
    Predicted Properties
    Property Value Source
    water solubility 9.77e-02 g/l ALOGPS
    logP 3.31 ALOGPS
    logP 4.52 ChemAxon
    logS -3.5 ALOGPS
    pKa (strongest acidic) 13.62 ChemAxon
    pKa (strongest basic) 8 ChemAxon
    physiological charge 1 ChemAxon
    hydrogen acceptor count 2 ChemAxon
    hydrogen donor count 1 ChemAxon
    polar surface area 32.34 ChemAxon
    rotatable bond count 5 ChemAxon
    refractivity 90.19 ChemAxon
    polarizability 34.19 ChemAxon
    References
    Synthesis Reference Not Available
    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
    Resource Link
    KEGG Compound C07529 Link_out
    PubChem Compound 2474 Link_out
    PubChem Substance 46506768 Link_out
    ChemSpider 2380 Link_out
    ChEBI 3215 Link_out
    ChEMBL 3215 Link_out
    Therapeutic Targets Database DAP001229 Link_out
    PharmGKB PA135057240 Link_out
    IUPHAR 2397 Link_out
    Guide to Pharmacology 2397 Link_out
    Drug Product Database 2165414 Link_out
    RxList http://www.rxlist.com/cgi/generic2/bupivacaine.htm Link_out
    Drugs.com http://www.drugs.com/cdi/bupivacaine-solution.html Link_out
    Wikipedia http://en.wikipedia.org/wiki/Bupivacaine Link_out
    ATC Codes
    • N01BB01
    • N01BB10
    AHFS Codes
    • 72:00.00
    PDB Entries Not Available
    FDA label show (147 KB)
    MSDS show (73.3 KB)
    Interactions
    Drug Interactions
    Drug Interaction
    Conivaptan Conivaptan 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 Interactions Not Available
    Targets

    1. Sodium channel protein type 10 subunit alpha

    Pharmacological action: yes
    Actions: inhibitor

    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 protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Its electrophysiological properties vary depending on the type of the associated beta subunits (in vitro). Plays a role in neuropathic pain mechanisms

    Organism class: human
    UniProt ID: Q9Y5Y9 Link_out
    Gene: SCN10A Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Pharmacological action: unknown
    Actions: other/unknown

    Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(q) proteins which activate a phosphatidylinositol-calcium second messenger system. May play a role as an important modulator of renal function. Implicated the smooth muscle contractile response to PGE2 in various tissues

    Organism class: human
    UniProt ID: P34995 Link_out
    Gene: PTGER1 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: substrate

    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

    UniProt ID: P08684 Link_out
    Gene: CYP3A4
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: substrate

    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

    UniProt ID: P05177 Link_out
    Gene: CYP1A2
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: substrate

    Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

    UniProt ID: P33261 Link_out
    Gene: CYP2C19 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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

    Actions: substrate

    Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

    UniProt ID: P10635 Link_out
    Gene: CYP2D6 Link_out
    Protein Sequence: FASTA
    Gene Sequence: FASTA
    SNPs: SNPJam Report Link_out

    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
    Comments
    Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19