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| Name | Bupivacaine | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00297 (APRD00247) | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Groups | approved | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Description | A widely used local anesthetic agent. [PubChem] |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Salts | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 2180-92-9 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 288.4277 Monoisotopic: 288.220163528 |
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| 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)
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| IUPAC Name |
1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
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| SMILES |
CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C
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| Mass Spec | show (8.44 KB) | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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.
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| 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Patents | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Properties | ||||||||||||||||||||||||||||||||||||||||||||||||||||
| State | solid | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Synthesis Reference | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| PDB Entries | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (147 KB) | |||||||||||||||||||||||||||||||||||||||||||||||||||
| MSDS | show (73.3 KB) | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Food Interactions | Not Available | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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1. Sodium channel protein type 10 subunit alpha Pharmacological action: yesActions: 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: humanUniProt ID: Q9Y5Y9 ![]() Gene: SCN10A ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Prostaglandin E2 receptor, EP1 subtype Pharmacological action: unknownActions: 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: humanUniProt ID: P34995 ![]() Gene: PTGER1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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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![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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![]() Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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![]() Gene: CYP2C19 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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