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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H28N2O.ClH
Molecular Weight 324.889
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOBUPIVACAINE HYDROCHLORIDE

SMILES

Cl.CCCCN1CCCC[C@H]1C(=O)NC2=C(C)C=CC=C2C

InChI

InChIKey=SIEYLFHKZGLBNX-NTISSMGPSA-N
InChI=1S/C18H28N2O.ClH/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);1H/t16-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C18H28N2O
Molecular Weight 288.4277
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18728849

Levobupivacaine (CHIROCAINE®) is a (S)-enantiomer of bupivacaine and it is related chemically and pharmacologically to the amino amide class of local anesthetics. Local anesthetics block the generation and the conduction of nerve impulses by increasing the threshold for electrical excitation in the nerve, by slowing propagation of the nerve impulse, and by reducing the rate of rise of the action potential. 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. Levobupivacaine (CHIROCAINE®) is a safer alternative for regional anesthesia than bupivacaine. It demonstrated less affinity and strength of depressant effects onto myocardial and central nervous vital centers in pharmacodynamic studies, and a superior pharmacokinetic profile.

Originator

Curator's Comment: Darwin Discovery Ltd., distributed by Purdue Pharma L.P.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.4 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CHIROCAINE

Approved Use

Chirocaine is indicated for the production of local or regional anesthesia for surgery and obstetrics, and for post-operative pain management.

Launch Date

9.3381119E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.474 μg/mL
1 mg/kg bw single, brachial plexus block
dose: 1 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
0.582 μg/mL
75 mg single, epidural
dose: 75 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
0.811 μg/mL
112.5 mg single, epidural
dose: 112.5 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
0.961 μg/mL
2 mg/kg bw single, brachial plexus block
dose: 2 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2.999 μg × h/mL
1 mg/kg bw single, brachial plexus block
dose: 1 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3.561 μg × h/mL
75 mg single, epidural
dose: 75 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
4.93 μg × h/mL
112.5 mg single, epidural
dose: 112.5 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
5.311 μg × h/mL
2 mg/kg bw single, brachial plexus block
dose: 2 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
3%
1 mg/kg bw single, brachial plexus block
dose: 1 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3%
75 mg single, epidural
dose: 75 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3%
112.5 mg single, epidural
dose: 112.5 mg
route of administration: Epidural
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
3%
2 mg/kg bw single, brachial plexus block
dose: 2 mg/kg bw
route of administration: Brachial plexus block
experiment type: SINGLE
co-administered:
LEVOBUPIVACAINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
142.5 mg single, intravenous
Dose: 142.5 mg
Route: intravenous
Route: single
Dose: 142.5 mg
Sources:
unhealthy, 77 years
n = 1
Health Status: unhealthy
Age Group: 77 years
Sex: F
Population Size: 1
Sources:
2 mg/kg single, caudal epidural
Dose: 2 mg/kg
Route: caudal epidural
Route: single
Dose: 2 mg/kg
Sources:
unhealthy, < 3 months
n = 22
Health Status: unhealthy
Age Group: < 3 months
Sex: M+F
Population Size: 22
Sources:
1.75 mg/kg single, subcutaneous
Dose: 1.75 mg/kg
Route: subcutaneous
Route: single
Dose: 1.75 mg/kg
Sources:
unhealthy, >66 years
n = 12
Health Status: unhealthy
Age Group: >66 years
Sex: M+F
Population Size: 12
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Levobupivacaine.
2001 Apr
Cardiac resuscitation after incremental overdosage with lidocaine, bupivacaine, levobupivacaine, and ropivacaine in anesthetized dogs.
2001 Jan
Does prior administration of enoxaparin influence the effects of levobupivacaine on blood clotting? Assessment using the Thrombelastograph.
2001 Jun
[Peripheral nerve block. An overview of new developments in an old technique].
2001 May
Systemic toxicity of levobupivacaine, bupivacaine, and ropivacaine during continuous intravenous infusion to nonpregnant and pregnant ewes.
2001 Nov
[Levobupivacaine in obstetric analgesia and anaesthesia].
2001 Sep
A comparison of epidural levobupivacaine 0.5% with or without epinephrine for lumbar spine surgery.
2001 Sep
Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.
2001 Sep
Local anaesthesia in elective inguinal hernia repair: a randomised, double-blind study comparing the efficacy of levobupivacaine with racemic bupivacaine.
2002
Cardiac and CNS toxicity of levobupivacaine: strengths of evidence for advantage over bupivacaine.
2002
Effects of levobupivacaine, ropivacaine and bupivacaine on HERG channels: stereoselective bupivacaine block.
2002 Dec
Safety and efficacy of levobupivacaine for postoperative pain relief after the surgical removal of impacted third molars: a comparison with lignocaine and adrenaline.
2002 Dec
Levobupivacaine versus racemic bupivacaine for spinal anesthesia.
2002 Jan
Levobupivacaina, bupivacaina racemica e ropivacaina nel blocco del plesso brachiale.
2002 Jul-Aug
A comparative study of the safety and efficacy of 0.5% levobupivacaine and 0.5% bupivacaine for epidural anesthesia in subjects undergoing elective caesarean section.
2002 Mar
Clinical properties of levobupivacaine or racemic bupivacaine for sciatic nerve block.
2002 Mar
Periosteal infusion of bupivacaine/morphine post sternal fracture: a new analgesic technique.
2002 May-Jun
The place of ropivacaine in anesthesia.
2003
A comparison of three different concentrations of levobupivacaine for caudal block in children.
2003 Aug
Comparison of different concentrations of levobupivacaine for post-operative epidural analgesia.
2003 Aug
A prospective, randomized, double-blind comparison of epidural levobupivacaine 0.5% with epidural ropivacaine 0.75% for lower limb procedures.
2003 Dec
Preincisional local infiltration of levobupivacaine vs ropivacaine for pain control after laparoscopic cholecystectomy.
2003 Dec
The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats.
2003 Jul
Convulsions following axillary brachial plexus blockade with levobupivacaine.
2003 Jun
Convulsions following axillary brachial plexus blockade with levobupivacaine.
2003 Jun
Intraoperative epidural anesthesia and postoperative analgesia with levobupivacaine for major orthopedic surgery: a double-blind, randomized comparison of racemic bupivacaine and ropivacaine.
2003 Mar
Urinary bladder scanning after day-case arthroscopy under spinal anaesthesia: comparison between lidocaine, ropivacaine, and levobupivacaine.
2003 Mar
[Prevention of cardiovascular accidents during locoregional anesthesia].
2003 May
Stability of sufentanil and levobupivacaine solutions and a mixture in a 0.9% sodium chloride infusion stored in polypropylene syringes.
2003 May
Comparison of the effects of intrathecal ropivacaine, levobupivacaine, and bupivacaine for Caesarean section.
2003 Nov
Onset time, quality of blockade, and duration of three-in-one blocks with levobupivacaine and bupivacaine.
2003 Sep
Severe phantom leg pain in an amputee after lumbar plexus block.
2003 Sep-Oct
A comparison of levobupivacaine 0.5% and racemic bupivacaine 0.5% for extradural anesthesia for caesarean section.
2003 Sep-Oct
Can ropivacaine and levobupivacaine be used as test doses during regional anesthesia?
2004 Apr
Pharmacokinetics of levobupivacaine 0.25% following caudal administration in children under 2 years of age.
2004 Feb
Levobupivacaine for pediatric spinal anesthesia.
2004 Jan
Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration.
2004 Jun
High-dose bupivacaine, levobupivacaine and ropivacaine in axillary brachial plexus block.
2004 May
Patents

Sample Use Guides

Surgical anaesthesia: epidural for surgery 10-20 mL (50-150 mg), epidural for cesarean section 20-30 mL (100-150 mg), peripheral nerve 30 mL or 0.4 mL/kg (75-150 mg or 1-2 mg/kg), ophthalmic 5-15 mL (37.5-112.5 mg), local infiltration 60 mL (150 mg). Pain management: epidural for labor analgesia 10-20 mL (25-50 mg), epidural for post-operative pain 4-10 mL/h (5-25 mg/h).
Route of Administration: Intravenous
The antagonist activity of levobupivacaine was tested at the human nicotinic acetylcholine (nACh), murine N-methyl-d-aspartate (NMDA), murine gamma-aminobutyric acid(A) (GABA(A)), and human 5-hydroxytryptamine(3A) (5-HT(3A)) receptors expressed in Xenopus oocytes using a 2-voltage clamp technique. The IC50 of levobupivacaine were 950 uM, 65 uM and 85 uM for NMDA, 5-HT(3A), and nACh receptors, respectively. Inhibition of the GABA(A) receptor required concentrations in excess of 10 mM.
Substance Class Chemical
Created
by admin
on Fri Dec 16 18:32:12 UTC 2022
Edited
by admin
on Fri Dec 16 18:32:12 UTC 2022
Record UNII
J998RDZ51I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LEVOBUPIVACAINE HYDROCHLORIDE
JAN   MART.   ORANGE BOOK   USAN   WHO-DD  
USAN  
Official Name English
BUPIVACAINE (-)-FORM HYDROCHLORIDE [MI]
Common Name English
(S)-1-BUTYL-N-(2,6-DIMETHYLPHENYL)-2-PIPERIDINECARBOXAMIDE MONOHYDROCHLORIDE
Systematic Name English
LEVOBUPIVACAINE HYDROCHLORIDE [JAN]
Common Name English
LEVOBUPIVACAINE HCL [VANDF]
Common Name English
LEVOBUPIVACAINE HYDROCHLORIDE [MART.]
Common Name English
LEVOBUPIVACAINE HYDROCHLORIDE [USAN]
Common Name English
(S)-1-BUTYL-2',6'-PIPECOLOXYLIDIDE MONOHYDROCHLORIDE
Common Name English
Levobupivacaine hydrochloride [WHO-DD]
Common Name English
LEVOBUPIVACAINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
CHIROCAINE
Code English
LEVOBUPIVACAINE HCL
VANDF  
Common Name English
BUPIVACAINE (-)-FORM HYDROCHLORIDE
MI  
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C245
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
Code System Code Type Description
ChEMBL
CHEMBL1201193
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
EPA CompTox
DTXSID9046071
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
FDA UNII
J998RDZ51I
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
EVMPD
SUB02904MIG
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
USAN
KK-63
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
NCI_THESAURUS
C61805
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
RXCUI
259454
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY RxNorm
MERCK INDEX
M2769
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY Merck Index
CAS
27262-48-2
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
DRUG BANK
DBSALT000834
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
PUBCHEM
117965
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
CHEBI
31772
Created by admin on Fri Dec 16 18:32:12 UTC 2022 , Edited by admin on Fri Dec 16 18:32:12 UTC 2022
PRIMARY
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PARENT -> SALT/SOLVATE
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