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Identification
NameLevorphanol
Accession NumberDB00854  (APRD00764)
TypeSmall Molecule
GroupsApproved
Description

A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
LevorfanolSpanishINN
LevorfanoloItalianDCIT
LévorphanolFrenchINN
LevorphanolGermanINN
LevorphanolumLatinINN
Prescription ProductsNot Available
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levorphanol Tartratetablet2 mgoralRoxane Laboratories, Inc2000-03-31Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
AromaroneNot Available
CetarinNot Available
LemoranNot Available
Levo-DromoranValeant Pharmaceuticals International
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Levorphanol tartrate
ThumbNot applicableDBSALT000935
Categories
CAS number77-07-6
WeightAverage: 257.3706
Monoisotopic: 257.177964363
Chemical FormulaC17H23NO
InChI KeyJAQUASYNZVUNQP-USXIJHARSA-N
InChI
InChI=1S/C17H23NO/c1-18-9-8-17-7-3-2-4-14(17)16(18)10-12-5-6-13(19)11-15(12)17/h5-6,11,14,16,19H,2-4,7-10H2,1H3/t14-,16+,17+/m0/s1
IUPAC Name
(1R,9R,10R)-17-methyl-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-trien-4-ol
SMILES
[H][C@@]12CCCC[C@@]11CCN(C)[C@@H]2CC2=C1C=C(O)C=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as morphinans. These are polycyclic compounds with a four-ring skeleton with three condensed six-member rings forming a partially hydrogenated phenanthrene moiety, one of which is aromatic while the two others are alicyclic.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassMorphinans
Sub ClassNot Available
Direct ParentMorphinans
Alternative Parents
Substituents
  • Morphinan
  • Benzylisoquinoline
  • Phenanthrene
  • Benzazocine
  • Tetralin
  • Aralkylamine
  • Benzenoid
  • Piperidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate
PharmacodynamicsLevorphanol is a potent synthetic opioid analgesic indicated for the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate. Levorphanol is similar to morphine in its actions, however it is up to 8 times more potent than morphine. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equianalgesic doses, and like many mu-opioid drugs, levorphanol produces euphoria or has a positive effect on mood in many individuals.
Mechanism of actionLike other mu-agonist opioids it is believed to act at receptors in the periventricular and periaqueductal gray matter in both the brain and spinal cord to alter the transmission and perception of pain.
AbsorptionLevorphanol is well absorbed after PO administration with peak plasma concentrations occurring approximately 1 hour after dosing.
Volume of distribution
  • 10 to 13 L/kg
Protein binding40%
Metabolism

Levorphanol is extensively metabolized in the liver and is eliminated as the glucuronide metabolite.

Route of eliminationNot Available
Half life11-16 hours
Clearance
  • 0.78 to 1.1 L/kg/hr
ToxicityLD50=150 mg/kg (orally in rats). Signs of overdose include nausea, emesis, dizziness, respiratory depression, hypotension, urinary retention, cardiac arrhythmias, allergic reactions, skin rash, and uticaria.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9924
Blood Brain Barrier+0.9953
Caco-2 permeable+0.8767
P-glycoprotein substrateSubstrate0.8217
P-glycoprotein inhibitor INon-inhibitor0.7866
P-glycoprotein inhibitor IINon-inhibitor0.935
Renal organic cation transporterInhibitor0.7666
CYP450 2C9 substrateNon-substrate0.7467
CYP450 2D6 substrateSubstrate0.78
CYP450 3A4 substrateSubstrate0.7112
CYP450 1A2 substrateNon-inhibitor0.6437
CYP450 2C9 substrateNon-inhibitor0.9139
CYP450 2D6 substrateInhibitor0.7703
CYP450 2C19 substrateNon-inhibitor0.8908
CYP450 3A4 substrateNon-inhibitor0.8856
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9051
Ames testNon AMES toxic0.5661
CarcinogenicityNon-carcinogens0.9694
BiodegradationNot ready biodegradable0.9681
Rat acute toxicity2.9455 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6841
hERG inhibition (predictor II)Non-inhibitor0.5153
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral2 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point198-199 °CPhysProp
water solubility1840 mg/LNot Available
logP3.11HANSCH,C ET AL. (1995)
pKa9.58SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.173 mg/mLALOGPS
logP3.29ALOGPS
logP2.9ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)10.46ChemAxon
pKa (Strongest Basic)9.66ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity78.08 m3·mol-1ChemAxon
Polarizability29.84 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraMS
References
Synthesis Reference

Joseph P. Haar, “Process for the Production of Levorphanol and Related Compounds.” U.S. Patent US20080146805, issued June 19, 2008.

US20080146805
General ReferenceNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (5.23 KB)
Interactions
Drug Interactions
Drug
AcetazolamideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
AlvimopanAnalgesics (Opioid) may enhance the adverse/toxic effect of Alvimopan. This is most notable for patients receiving long-term (i.e., more than 7 days) opiates prior to alvimopan initiation.
AmilorideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
Ammonium chlorideMay increase the excretion of Analgesics (Opioid).
AmphetamineMay enhance the analgesic effect of Analgesics (Opioid).
BendroflumethiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
BumetanideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
CathinoneMay enhance the analgesic effect of Analgesics (Opioid).
ChlorothiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
ChlorthalidoneAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
CyclothiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
DesmopressinAnalgesics (Opioid) may enhance the adverse/toxic effect of Desmopressin.
DoxylamineMay enhance the CNS depressant effect of CNS Depressants.
DronabinolMay enhance the CNS depressant effect of CNS Depressants.
DroperidolMay enhance the CNS depressant effect of CNS Depressants.
Ethacrynic acidAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
EthoxzolamideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
FurosemideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
HydrochlorothiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
HydrocodoneCNS Depressants may enhance the CNS depressant effect of Hydrocodone.
HydroflumethiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
HydroxyzineMay enhance the CNS depressant effect of CNS Depressants.
IndapamideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
Magnesium SulfateMay enhance the CNS depressant effect of CNS Depressants.
MethotrimeprazineCNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.
MetolazoneAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
MetyrosineCNS Depressants may enhance the sedative effect of Metyrosine.
MirtazapineCNS Depressants may enhance the CNS depressant effect of Mirtazapine.
NabiloneMay enhance the CNS depressant effect of CNS Depressants.
NaltrexoneMay diminish the therapeutic effect of Analgesics (Opioid).
OrphenadrineCNS Depressants may enhance the CNS depressant effect of Orphenadrine.
PegvisomantAnalgesics (Opioid) may diminish the therapeutic effect of Pegvisomant.
PerampanelMay enhance the CNS depressant effect of CNS Depressants.
PramipexoleCNS Depressants may enhance the sedative effect of Pramipexole.
RopiniroleCNS Depressants may enhance the sedative effect of ROPINIRole.
RotigotineCNS Depressants may enhance the sedative effect of Rotigotine.
RufinamideMay enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
SpironolactoneAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
SuccinylcholineMay enhance the bradycardic effect of Analgesics (Opioid).
SuvorexantCNS Depressants may enhance the CNS depressant effect of Suvorexant.
TapentadolMay enhance the CNS depressant effect of CNS Depressants.
ThalidomideCNS Depressants may enhance the CNS depressant effect of Thalidomide.
TicrynafenAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
TorasemideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
TriamtereneAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
TrichlormethiazideAnalgesics (Opioid) may enhance the adverse/toxic effect of Diuretics.
ZolpidemCNS Depressants may enhance the CNS depressant effect of Zolpidem.
Food Interactions
  • Take without regard to meals. Avoid alcohol.

Targets

1. Mu-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Mu-type opioid receptor P35372 Details

References:

  1. Allen RM, Granger AL, Dykstra LA: The competitive N-methyl-D-aspartate receptor antagonist (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959) potentiates the antinociceptive effects of opioids that vary in efficacy at the mu-opioid receptor. J Pharmacol Exp Ther. 2003 Nov;307(2):785-92. Epub 2003 Sep 15. Pubmed
  2. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. Pubmed

2. Delta-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Delta-type opioid receptor P41143 Details

References:

  1. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. Pubmed

3. Kappa-type opioid receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Kappa-type opioid receptor P41145 Details

References:

  1. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on October 20, 2013 13:28