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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
Salts
Name/CAS Structure Properties
Levorphanol tartrate
Thumb Not applicable DBSALT000935
Brand names
NameCompany
AromaroneNot Available
CetarinNot Available
LemoranNot Available
Levo-DromoranValeant Pharmaceuticals International
Brand mixturesNot Available
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[7.5.3.0^{1,10}.0^{2,7}]heptadeca-2(7),3,5-trien-4-ol
SMILES
[H][C@@]12CCCC[C@@]11CCN(C)[C@@H]2CC2=C1C=C(O)C=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassMorphinans
SubclassNot Available
Direct parentMorphinans
Alternative parentsBenzylisoquinolines; Phenanthrenes and Derivatives; Tetralins; Phenols and Derivatives; Piperidines; Tertiary Amines; Enols; Polyamines
Substituentsphenanthrene; tetralin; phenol derivative; piperidine; benzene; tertiary amine; enol; polyamine; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 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.
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
Pathways
PathwayCategorySMPDB ID
Levorphanol Action PathwayDrug actionSMP00673
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9924
Blood Brain Barrier + 0.9953
Caco-2 permeable + 0.8767
P-glycoprotein substrate Substrate 0.8217
P-glycoprotein inhibitor I Non-inhibitor 0.7866
P-glycoprotein inhibitor II Non-inhibitor 0.935
Renal organic cation transporter Inhibitor 0.7666
CYP450 2C9 substrate Non-substrate 0.7467
CYP450 2D6 substrate Substrate 0.78
CYP450 3A4 substrate Substrate 0.7112
CYP450 1A2 substrate Non-inhibitor 0.6437
CYP450 2C9 substrate Non-inhibitor 0.9139
CYP450 2D6 substrate Inhibitor 0.7703
CYP450 2C19 substrate Non-inhibitor 0.8908
CYP450 3A4 substrate Non-inhibitor 0.8856
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9051
Ames test Non AMES toxic 0.5661
Carcinogenicity Non-carcinogens 0.9694
Biodegradation Not ready biodegradable 0.9681
Rat acute toxicity 2.9455 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.6841
hERG inhibition (predictor II) Non-inhibitor 0.5153
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
Injection, solutionIntramuscular
Injection, solutionIntravenous
Injection, solutionSubcutaneous
TabletOral
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 Solubility0.173ALOGPS
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 RuleNoChemAxon
Spectra
Spectra
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
ResourceLink
KEGG CompoundC08014
BindingDB50017233
Therapeutic Targets DatabaseDAP000268
PharmGKBPA164744368
RxListhttp://www.rxlist.com/cgi/generic2/levorphanol.htm
Drugs.comhttp://www.drugs.com/cdi/levorphanol.html
WikipediaLevorphanol
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(5.23 KB)
Interactions
Drug Interactions
Drug
AlvimopanIncreases levels by receptor binding competition. Discontinue opioid administration at least 7 days prior to administrating Alvimopan.
EltrombopagIncreases levels of Levorphanol via metabolism decrease. UDP-glucuronosyltransferase inhibition with unclear significance.
TriprolidineThe CNS depressants, Triprolidine and Levorphanol, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
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