ContaminantDB: Bupivacaine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Targets (2)XML

Record Information

Version

1.0

Creation Date

2009-07-21 20:26:32 UTC

Update Date

2026-03-26 18:38:32 UTC

Accession Number

CHEM002164

Identification

Common Name

Bupivacaine

Class

Small Molecule

Description

Bupivacaine 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.

Contaminant Sources

HMDB Contaminants - Urine
STOFF IDENT Compounds
T3DB toxins

Contaminant Type

Amide
Amine
Anesthetic, Local
Drug
Metabolite
Organic Compound
Synthetic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Bupivacaina	ChEBI
Bupivacainum	ChEBI
DL-Bupivacaine	ChEBI
Marcaine	ChEBI
Bucaine	Kegg
Exparel	Kegg
(+-)-Bupivacaine	HMDB
Bloqueina	HMDB
Bupivacaine HCL	HMDB
Bupivacaine HCL kit	HMDB
CBupivacaine	HMDB
DUR-843	HMDB
LAC-43	HMDB
Braun, bupivacaina	MeSH, HMDB
Bupivacaine carbonate	MeSH, HMDB
Bupivacaine monohydrochloride, monohydrate	MeSH, HMDB
Strathmann brand OF bupivacaine hydrochloride	MeSH, HMDB
Abbott brand OF bupivacaine hydrochloride	MeSH, HMDB
Astra brand OF bupivacaine hydrochloride	MeSH, HMDB
Carbostesin	MeSH, HMDB
Dolanaest	MeSH, HMDB
Inibsa brand OF bupivacaine hydrochloride	MeSH, HMDB
Janapharm, bupivacain	MeSH, HMDB
1-Butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide	MeSH, HMDB
Anhydrous, bupivacaine	MeSH, HMDB
Bupivacain janapharm	MeSH, HMDB
Bupivacain-RPR	MeSH, HMDB
Bupivacaina braun	MeSH, HMDB
Bupivacaine anhydrous	MeSH, HMDB
Bupivacaine hydrochloride	MeSH, HMDB
Carbonate, bupivacaine	MeSH, HMDB
Jenapharm brand OF bupivacaine hydrochloride	MeSH, HMDB
Sensorcaine	MeSH, HMDB
AstraZeneca brand OF bupivacaine hydrochloride	MeSH, HMDB
Aventis brand OF bupivacaine hydrochloride	MeSH, HMDB
Braun brand OF bupivacaine hydrochloride	MeSH, HMDB
Bupivacain RPR	MeSH, HMDB
Buvacaina	MeSH, HMDB
Hydrochloride, bupivacaine	MeSH, HMDB
Marcain	MeSH, HMDB
Pisa brand OF bupivacaine hydrochloride	MeSH, HMDB
Svedocain sin vasoconstr	MeSH, HMDB

Chemical Formula

C₁₈H₂₈N₂O

Average Molecular Mass

288.428 g/mol

Monoisotopic Mass

288.220 g/mol

CAS Registry Number

2180-92-9

IUPAC Name

1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide

Traditional Name

bupivacaine

SMILES

CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C

InChI Identifier

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)

InChI Key

LEBVLXFERQHONN-UHFFFAOYSA-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.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Alpha 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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

piperidinecarboxamide (CHEBI:77431 )
tertiary amino compound (CHEBI:77431 )
aromatic amide (CHEBI:77431 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Caveolae
Cytosol
Endoplasmic reticulum
Extracellular
Membrane
Mitochondrion
Nerve Fiber
Plasma Membrane
Sarcoplasm
Sarcoplasmic Reticulum

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Apoptosis	Not Available	map04210
Fatty acid Metabolism	SMP00051	map00071
Antiarrhythmic Drugs	Not Available	Not Available
Bupivacaine Pathway	Not Available	Not Available

Applications

Biological Roles

Chemical Roles

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	107-108°C
Boiling Point	Not Available
Solubility	2400 mg/L (at 25°C)

Predicted Properties

Property	Value	Source
Water Solubility	0.098 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 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	90.19 m³·mol⁻¹	ChemAxon
Polarizability	34.19 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-006t-6920000000-20e4e8d5c09a52a31c75	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-000i-0290000000-c1dbebb634be5e7e1140	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0006-0910000000-ae34de204bcb9a9deb23	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0006-0900000000-7ea7001506aae0c271a0	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0006-2900000000-ef819c5e235d6d524d8c	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-0006-7900000000-22d7491053c05d773e93	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QFT , positive	splash10-001l-9400000000-71357b8186126c5933ce	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 90V, Positive	splash10-001l-9400000000-f152216f702642a2a96b	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 15V, Positive	splash10-000i-0290000000-473772a88887df5462f7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 45V, Positive	splash10-0006-0900000000-73c58abee6a70ae243ed	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 30V, Positive	splash10-0006-0910000000-2d35aaa0fbbc69b60c7d	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 60V, Positive	splash10-0006-2900000000-c1144b59f68c25239771	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 75V, Positive	splash10-0006-7900000000-a4b8408dc9df27267589	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0079-0970000000-e665f05dc8da9fafd8f0	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00dl-2900000000-6396ddc6fc9d5e9b6c64	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0ac0-9200000000-befeaee90e72918d68b3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0290000000-e01610a30f93d9c5ec2a	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00ri-0970000000-e26949f880557c6da815	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00xr-3900000000-56dfe5d9cd7f629f17e3	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0090000000-e83ab5b70775090159b7	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000i-0690000000-6ff0193988455d286726	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-00xr-1920000000-87f1897c4a60793791d5	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0190000000-23ffc562239624515183	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000g-3920000000-6aaf7d8f5f0149cec33e	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0007-8900000000-e62af4b8065c6c1caf01	Spectrum

Toxicity Profile

Route of Exposure

Epidural, 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 Toxicity

Bupivacaine 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.

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. 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 Values

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. LD50: 6 to 8 mg/kg (intravenous, mice) LD50: 38 to 54 mg/kg (subcutaneous, mice)

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

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.

Minimum Risk Level

Not Available

Health Effects

Acute 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.

Symptoms

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.

Treatment

If 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.

Concentrations

Not Available

External Links

DrugBank ID

DB00297

HMDB ID

HMDB0243533

FooDB ID

Not Available

Phenol Explorer ID

Not Available

KNApSAcK ID

Not Available

BiGG ID

Not Available

BioCyc ID

Not Available

METLIN ID

Not Available

PDB ID

Not Available

Wikipedia Link

Bupivacaine

Chemspider ID

2380

ChEBI ID

77431

PubChem Compound ID

Not Available

Kegg Compound ID

C07529

YMDB ID

Not Available

ECMDB ID

Not 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.

MSDS

Link

General References

Not Available

Bupivacaine (CHEM002164)

Structure for CHEM002164: Bupivacaine