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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
Levorfanol
Levorfanolo
Lévorphanol
Levorphanol
Levorphanolum
External Identifiers
  • Dea No. 9220
  • Dea No. 9733
  • Ro 1-5431
Approved Prescription ProductsNot Available
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levorphanol Tartratetablet2 mg/1oralRoxane Laboratories, Inc2000-03-31Not applicableUs
Levorphanol Tartratetablet2 mg/1oralSentynl Therapeutics, Inc.2015-05-28Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not 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
UNII27618J1N2X
CAS number77-07-6
WeightAverage: 257.3706
Monoisotopic: 257.177964363
Chemical FormulaC17H23NO
InChI KeyInChIKey=JAQUASYNZVUNQP-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.
Related Articles
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
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 inhibitorNon-inhibitor0.9139
CYP450 2D6 inhibitorInhibitor0.7703
CYP450 2C19 inhibitorNon-inhibitor0.8908
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Valeant pharmaceuticals international
  • Roxane laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral2 mg/1
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
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-0a4i-5930000000-4593c62f1e2a0579a248View in MoNA
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 ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (5.23 KB)
Interactions
Drug Interactions
Drug
AcepromazineAcepromazine may increase the hypotensive activities of Levorphanol.
AcetazolamideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Acetazolamide.
AlvimopanThe risk or severity of adverse effects can be increased when Levorphanol is combined with Alvimopan.
AmilorideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Amiloride.
Ammonium chlorideAmmonium chloride may increase the excretion rate of Levorphanol which could result in a higher serum level.
AmphetamineAmphetamine may increase the analgesic activities of Levorphanol.
AzelastineLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Levorphanol.
BendroflumethiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Bendroflumethiazide.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
BumetanideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Bumetanide.
ButorphanolButorphanol may decrease the analgesic activities of Levorphanol.
CathinoneCathinone may increase the analgesic activities of Levorphanol.
ChlorothiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Chlorothiazide.
ChlorthalidoneThe risk or severity of adverse effects can be increased when Levorphanol is combined with Chlorthalidone.
CyclothiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Cyclothiazide.
DesmopressinThe risk or severity of adverse effects can be increased when Levorphanol is combined with Desmopressin.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
EluxadolineLevorphanol may increase the activities of Eluxadoline.
Etacrynic acidThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ethacrynic acid.
EthanolLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
EthoxzolamideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ethoxzolamide.
FurosemideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Furosemide.
HydrochlorothiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Hydrochlorothiazide.
HydrocodoneLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroflumethiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Hydroflumethiazide.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
IndapamideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Indapamide.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Levorphanol.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
MethotrimeprazineLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetolazoneThe risk or severity of adverse effects can be increased when Levorphanol is combined with Metolazone.
MetyrosineLevorphanol may increase the sedative activities of Metyrosine.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
MirtazapineLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
NaltrexoneThe therapeutic efficacy of Levorphanol can be decreased when used in combination with Naltrexone.
OrphenadrineLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineLevorphanol may increase the serotonergic activities of Paroxetine.
PegvisomantThe therapeutic efficacy of Pegvisomant can be decreased when used in combination with Levorphanol.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
PramipexoleLevorphanol may increase the sedative activities of Pramipexole.
ProcyclidineThe risk or severity of adverse effects can be increased when Procyclidine is combined with Levorphanol.
RamosetronLevorphanol may increase the activities of Ramosetron.
RopiniroleLevorphanol may increase the sedative activities of Ropinirole.
RotigotineLevorphanol may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Levorphanol.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
SpironolactoneThe risk or severity of adverse effects can be increased when Levorphanol is combined with Spironolactone.
SuccinylcholineSuccinylcholine may increase the bradycardic activities of Levorphanol.
SuvorexantLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Levorphanol.
ThalidomideLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
TicrynafenThe risk or severity of adverse effects can be increased when Levorphanol is combined with Ticrynafen.
TorasemideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Torasemide.
TriamtereneThe risk or severity of adverse effects can be increased when Levorphanol is combined with Triamterene.
TrichlormethiazideThe risk or severity of adverse effects can be increased when Levorphanol is combined with Trichlormethiazide.
ZolpidemLevorphanol may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food Interactions
  • Take without regard to meals. Avoid alcohol.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociati...
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
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:12975489 ]
  2. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. [PubMed:17039381 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurot...
Gene Name:
OPRD1
Uniprot ID:
P41143
Molecular Weight:
40368.235 Da
References
  1. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. [PubMed:17039381 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Opioid receptor activity
Specific Function:
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates th...
Gene Name:
OPRK1
Uniprot ID:
P41145
Molecular Weight:
42644.665 Da
References
  1. Prommer E: Levorphanol: the forgotten opioid. Support Care Cancer. 2007 Mar;15(3):259-64. Epub 2006 Oct 13. [PubMed:17039381 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on October 20, 2013 13:28