Identification

Name
Levorphanol
Accession Number
DB00854  (APRD00764)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • Levorfanol
  • Levorfanolo
  • Lévorphanol
  • Levorphanol
  • Levorphanolum
External IDs
Dea No. 9220 / Dea No. 9733 / IDS-NL-007 / RO 1-5431
Product Ingredients
IngredientUNIICASInChI Key
Levorphanol tartrate04WQU6T9QINot AvailableUMZNDVASJKIQCB-QLFXFZCRSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levo-DromoranInjection, solution2 mg/1mLParenteralValeant Pharmaceuticals North America1953-01-082014-12-04Us
Levo-DromoranTablet2 mg/1OralValeant Pharmaceuticals North America1953-01-082014-12-04Us
Levo-DromoranInjection, solution2 mg/1mLParenteralValeant Pharmaceuticals North America1953-01-082014-12-04Us
Levorphanol TartrateTablet2 mg/1OralRoxane Laboratories, Inc.2006-06-022006-06-02Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levorphanol TartrateTablet3 mg/1OralSentynl Therapeutics, Inc.2018-06-18Not applicableUs
Levorphanol TartrateTablet2 mg/1OralRoxane Laboratories2000-03-312017-12-16Us
Levorphanol TartrateTablet1 mg/1OralSentynl Therapeutics, Inc.2018-06-18Not applicableUs
Levorphanol TartrateTablet2 mg/1OralSentynl Therapeutics, Inc.2000-03-31Not applicableUs
International/Other Brands
Aromarone / Cetarin / Lemoran / Levo-Dromoran (Valeant Pharmaceuticals International)
Categories
UNII
27618J1N2X
CAS number
77-07-6
Weight
Average: 257.3706
Monoisotopic: 257.177964363
Chemical Formula
C17H23NO
InChI Key
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

Pharmacology

Indication

For the management of moderate to severe pain or as a preoperative medication where an opioid analgesic is appropriate.

Associated Conditions
Pharmacodynamics

Levorphanol 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 action

Like 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.

TargetActionsOrganism
AMu-type opioid receptor
agonist
Human
UDelta-type opioid receptor
agonist
Human
UKappa-type opioid receptor
agonist
Human
Absorption

Levorphanol 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 binding

40%

Metabolism

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

Route of elimination
Not Available
Half life

11-16 hours

Clearance
  • 0.78 to 1.1 L/kg/hr
Toxicity

LD50=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
PathwayCategory
Levorphanol Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Levorphanol is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Levorphanol is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of serotonin syndrome can be increased when Levorphanol is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
AcepromazineThe risk or severity of hypotension and central nervous system depression can be increased when Acepromazine is combined with Levorphanol.
AceprometazineThe risk or severity of hypotension and central nervous system depression can be increased when Aceprometazine is combined with Levorphanol.
Food Interactions
  • Take without regard to meals. Avoid alcohol.

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 References
Not Available
External Links
Human Metabolome Database
HMDB0014992
KEGG Drug
D08123
KEGG Compound
C08014
PubChem Compound
5359272
PubChem Substance
46506558
ChemSpider
16736212
BindingDB
50017233
ChEBI
6444
ChEMBL
CHEMBL592
Therapeutic Targets Database
DAP000268
PharmGKB
PA164744368
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Levorphanol
MSDS
Download (5.23 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingSupportive CareMetastatic Malignant Neoplasm / Neoplasms, Malignant / Pain NOS1
Not AvailableCompletedNot AvailablePain, Chronic1

Pharmacoeconomics

Manufacturers
  • Valeant pharmaceuticals international
  • Roxane laboratories inc
Packagers
  • Cardinal Health
  • Legacy Pharmaceuticals Packaging LLC
  • Roxane Labs
  • Valeant Ltd.
Dosage forms
FormRouteStrength
Injection, solutionParenteral2 mg/1mL
TabletOral2 mg/1
TabletOral1 mg/1
TabletOral3 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)198-199 °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 RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0a4i-5930000000-4593c62f1e2a0579a248
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Morphinans
Sub Class
Not Available
Direct Parent
Morphinans
Alternative Parents
Phenanthrenes and derivatives / Benzazocines / Tetralins / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
show 1 more
Substituents
Morphinan / Phenanthrene / Benzazocine / Tetralin / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Piperidine / Benzenoid / Tertiary aliphatic amine / Tertiary amine
show 10 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
morphinane alkaloid (CHEBI:6444)

Targets

Details
1. Mu-type opioid receptor
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...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
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 n...
Gene Name
OPRD1
Uniprot ID
P41143
Uniprot Name
Delta-type opioid receptor
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 synt...
Gene Name
OPRK1
Uniprot ID
P41145
Uniprot Name
Kappa-type opioid receptor
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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:44