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Record Information
Version2.0
Creation Date2009-07-21 20:26:32 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2742
Identification
Common NameBupivacaine
ClassSmall Molecule
DescriptionBupivacaine is only found in individuals that have used or taken this drug. It is a widely used local anesthetic agent. Bupivacaine 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. 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.
Compound Type
  • Amide
  • Amine
  • Anesthetic, Local
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+-)-Bupivacaine
(RS)-bupivacaine
1-Butyl-2',6'-pipecoloxylidide
1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide
Bloqueina
Bupivacaina
Bupivacaine HCL
Bupivacaine HCL KIT
Bupivacainum
Bupivan
Carbostesin
CBupivacaine
dl-1-Butyl-2',6'-pipecoloxylidide
DL-Bupivacaine
DUR-843
EXPAREL
LAC-43
Marcain
Marcaina
Marcaine
Racemic bupivacaine
Sensorcaine
Sensorcaine-MPF
Vivacaine
Chemical FormulaC18H28N2O
Average Molecular Mass288.428 g/mol
Monoisotopic Mass288.220 g/mol
CAS Registry Number2180-92-9
IUPAC Name1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
Traditional Namebupivacaine
SMILESCCCCN1CCCCC1C(O)=NC1=C(C)C=CC=C1C
InChI IdentifierInChI=1/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)
InChI KeyInChIKey=LEBVLXFERQHONN-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • 2-piperidinecarboxamide
  • Piperidinecarboxamide
  • Anilide
  • M-xylene
  • Xylene
  • N-arylamide
  • Monocyclic benzene moiety
  • Benzenoid
  • Piperidine
  • Carboxamide group
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Azacycle
  • Organoheterocyclic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Caveolae
  • Cytosol
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
  • Mitochondrion
  • Nerve Fiber
  • Plasma Membrane
  • Sarcoplasm
  • Sarcoplasmic Reticulum
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Fatty acid MetabolismSMP00051 map00071
Antiarrhythmic DrugsNot AvailableNot Available
Bupivacaine PathwayNot AvailableNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point107-108°C
Boiling PointNot Available
Solubility2400 mg/L (at 25°C)
LogP3.41
Predicted Properties
PropertyValueSource
Water Solubility0.098 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 Area32.34 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity90.19 m³·mol⁻¹ChemAxon
Polarizability34.19 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006t-6920000000-20e4e8d5c09a52a31c75JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-0290000000-c1dbebb634be5e7e1140JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-0910000000-ae34de204bcb9a9deb23JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-0900000000-7ea7001506aae0c271a0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-2900000000-ef819c5e235d6d524d8cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0006-7900000000-22d7491053c05d773e93JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001l-9400000000-71357b8186126c5933ceJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-0970000000-e665f05dc8da9fafd8f0JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dl-2900000000-6396ddc6fc9d5e9b6c64JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0ac0-9200000000-befeaee90e72918d68b3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0290000000-e01610a30f93d9c5ec2aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00ri-0970000000-e26949f880557c6da815JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00xr-3900000000-56dfe5d9cd7f629f17e3JSpectraViewer
Toxicity Profile
Route of ExposureEpidural, Intraspinal, Infiltration. 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.
Mechanism of ToxicityBupivacaine is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismAmide-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. 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
Toxicity ValuesThe 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. LD50: 6 to 8 mg/kg (intravenous, mice) LD50: 38 to 54 mg/kg (subcutaneous, mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsRecent 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.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00297
HMDB IDHMDB14442
PubChem Compound ID2474
ChEMBL IDCHEMBL1098
ChemSpider ID2380
KEGG IDC07529
UniProt IDNot Available
OMIM ID
ChEBI ID3215
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBupivacaine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBupivacaine
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.

MSDSLink
General References
  1. Picard J, Meek T: Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia. 2006 Feb;61(2):107-9. [16430560 ]
  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. [16810015 ]
  3. Drugs.com [Link]
  4. eMedicine (2008). Local Anesthetics. [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated GenesNot Available

Targets

General Function:
Prostaglandin e receptor activity
Specific Function:
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.
Gene Name:
PTGER1
Uniprot ID:
P34995
Molecular Weight:
41800.655 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. [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. [17016423 ]
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 across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:
SCN10A
Uniprot ID:
Q9Y5Y9
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. [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. [17016423 ]