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Identification
NameRopivacaine
Accession NumberDB00296  (APRD00492)
Typesmall molecule
Groupsapproved
Description

Ropivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the trade name Naropin. [Wikipedia]

Structure
Thumb
Synonyms
SynonymLanguageCode
(S)-(−)-1-propyl-2',6'-pipecoloxylidideNot AvailableNot Available
(S)-ropivacaineNot AvailableNot Available
L-N-n-propylpipecolic acid-2,6-xylidideNot AvailableNot Available
RopivacainaSpanishNot Available
RopivacaineNot AvailableINN
RopivacainumLatinINN
Salts
Name/CAS Structure Properties
Ropivacaine hydrochloride
Thumb Not applicable DBSALT000902
Brand names
NameCompany
NaropinAstraZeneca
Brand mixturesNot Available
Categories
CAS number84057-95-4
WeightAverage: 274.4011
Monoisotopic: 274.204513464
Chemical FormulaC17H26N2O
InChI KeyZKMNUMMKYBVTFN-GGYSOQFKNA-N
InChI
InChI=1/C17H26N2O/c1-4-11-19-12-6-5-10-15(19)17(20)18-16-13(2)8-7-9-14(16)3/h7-9,15H,4-6,10-12H2,1-3H3,(H,18,20)/t15-/s2
IUPAC Name
(2S)-N-(2,6-dimethylphenyl)-1-propylpiperidine-2-carboxamide
SMILES
CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C
Mass SpecNot Available
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
IndicationUsed in obstetric anesthesia and regional anesthesia for surgery.
PharmacodynamicsRopivacaine, a local anesthetic agent, is indicated 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.
Mechanism of actionLocal anesthetics such as Ropivacaine 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. Specifically, they block the sodium-channel and decrease chances of depolarization and consequent action potentials. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers.
AbsorptionBioavailability is 87%–98% following epidural administration.
Volume of distributionNot Available
Protein binding94%, mainly to a1-acid glycoprotein
Metabolism

Hepatic

SubstrateEnzymesProduct
Ropivacaine
3-hydroxyropivacaineDetails
Route of eliminationRopivacaine is extensively metabolized in the liver, predominantly by aromatic hydroxylation mediated by cytochrome P4501A to 3-hydroxy ropivacaine. After a single IV dose approximately 37% of the total dose is excreted in the urine as both free and conjugated 3-hydroxy ropivacaine. In total, 86% of the ropivacaine dose is excreted in the urine after intravenous administration of which only 1% relates to unchanged drug.
Half lifeApproximately 4.2 hours.
Clearance
  • 387 +/- 107 mL/min
  • unbound plasma clearance=7.2 +/- 1.6 L/min
ToxicitySystemic exposure to excessive quantities of ropivacaine mainly result in central nervous system (CNS) and cardiovascular effects – CNS effects usually occur at lower blood plasma concentrations and additional cardiovascular effects present at higher concentrations, though cardiovascular collapse may also occur with low concentrations. CNS effects may include CNS excitation (nervousness, tingling around the mouth, tinnitus, tremor, dizziness, blurred vision, seizures) followed by depression (drowsiness, loss of consciousness, respiratory depression and apnea). Cardiovascular effects include hypotension, bradycardia, arrhythmias, and/or cardiac arrest – some of which may be due to hypoxemia secondary to respiratory depression.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Ropivacaine Action PathwayDrug actionSMP00404
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9705
Blood Brain Barrier + 0.9377
Caco-2 permeable + 0.5912
P-glycoprotein substrate Substrate 0.8037
P-glycoprotein inhibitor I Inhibitor 0.8768
P-glycoprotein inhibitor II Non-inhibitor 0.6339
Renal organic cation transporter Non-inhibitor 0.6611
CYP450 2C9 substrate Non-substrate 0.819
CYP450 2D6 substrate Substrate 0.8919
CYP450 3A4 substrate Substrate 0.723
CYP450 1A2 substrate Non-inhibitor 0.5499
CYP450 2C9 substrate Non-inhibitor 0.9246
CYP450 2D6 substrate Inhibitor 0.8821
CYP450 2C19 substrate Non-inhibitor 0.8773
CYP450 3A4 substrate Non-inhibitor 0.5902
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6116
Ames test Non AMES toxic 0.8507
Carcinogenicity Non-carcinogens 0.8763
Biodegradation Not ready biodegradable 0.9783
Rat acute toxicity 2.2964 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8009
hERG inhibition (predictor II) Inhibitor 0.8438
Pharmacoeconomics
Manufacturers
  • App pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
SolutionEpidural
Prices
Unit descriptionCostUnit
Ropivacaine hcl-ns 0.5%1.84USDml
Ropivacaine hcl 0.2% on-q pump0.99USDml
Naropin 10 mg/ml ampule0.97USDml
Ropivacaine hcl-ns 0.3%0.9USDml
Ropivacaine-ns 0.1% on-q pump0.71USDml
Naropin 7.5 mg/ml ampule0.62USDml
Naropin 5 mg/ml vial0.58USDml
Ropivacaine hcl-ns 0.15%0.51USDml
Ropivacaine hcl-ns 0.125%0.48USDml
Naropin 5 mg/ml ampule0.46USDml
Naropin 2 mg/ml ampule0.44USDml
Ropivacaine hcl-ns 0.1%0.39USDml
Ropivacaine hcl-ns 0.25%0.34USDml
Ropivacaine hcl-ns 0.2%0.29USDml
Naropin 2 mg/ml infusion btl0.23USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States56705241994-05-262014-05-26
United States48700861993-09-242010-09-24
Canada21654462005-07-052014-05-26
Canada13375491995-11-142012-11-14
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility57.6 mg/LNot Available
logP2.90HANSCH,C ET AL. (1995)
pKa8.07Not Available
Predicted Properties
PropertyValueSource
water solubility2.53e-01 g/lALOGPS
logP2.91ALOGPS
logP4.07ChemAxon
logS-3ALOGPS
pKa (strongest acidic)13.62ChemAxon
pKa (strongest basic)7.82ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count1ChemAxon
polar surface area32.34ChemAxon
rotatable bond count4ChemAxon
refractivity85.59ChemAxon
polarizability32.67ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Peter Jaksch, “Process for the preparation of ropivacaine hydrochloride monohydrate.” U.S. Patent US5959112, issued February, 1970.

US5959112
General Reference
  1. Weinberg G, Ripper R, Feinstein DL, Hoffman W: Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003 May-Jun;28(3):198-202. Pubmed
  2. 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
  3. 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
External Links
ResourceLink
KEGG CompoundC07532
ChEBI8890
ChEMBLCHEMBL1077896
Therapeutic Targets DatabaseDAP001230
PharmGKBPA451271
Drug Product Database2229418
RxListhttp://www.rxlist.com/cgi/generic2/ropiva.htm
Drugs.comhttp://www.drugs.com/cdi/ropivacaine.html
WikipediaRopivacaine
ATC CodesN01BB09
AHFS Codes
  • 72:00.00
PDB EntriesNot Available
FDA labelshow(274 KB)
MSDSshow(57 KB)
Interactions
Drug Interactions
Drug
FluvoxamineIncreases the effect and toxicity of ropivacaine
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. Liu BG, Zhuang XL, Li ST, Xu GH: The effects of ropivacaine on sodium currents in dorsal horn neurons of neonatal rats. Anesth Analg. 2000 May;90(5):1034-8. Pubmed

Enzymes

1. Cytochrome P450 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 1A2 P05177 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Arlander E, Ekstrom G, Alm C, Carrillo JA, Bielenstein M, Bottiger Y, Bertilsson L, Gustafsson LL: Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther. 1998 Nov;64(5):484-91. Pubmed
  3. 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 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 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 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

4. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 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 September 25, 2013 19:00