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Identification
NameLevallorphan
Accession NumberDB00504  (APRD00733)
TypeSmall Molecule
GroupsApproved
DescriptionAn opioid antagonist with properties similar to those of naloxone; in addition it also possesses some agonist properties. It should be used cautiously; levallorphan reverses severe opioid-induced respiratory depression but may exacerbate respiratory depression such as that induced by alcohol or other non-opioid central depressants. (From Martindale, The Extra Pharmacopoeia, 30th ed, p683)
Structure
Thumb
Synonyms
Levallofano
Levallorphan
Lévallorphane
Levallorphanum
Levalorfano
Lorfan
Naloxiphan
External Identifiers
  • HSDB 2148
  • Ro-1-7700
  • UNII-U0VSF7HTN0
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
LorfanTakeda
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Levallorphan Tartrate
ThumbNot applicableDBSALT001040
Categories
UNII353613BU4U
CAS number152-02-3
WeightAverage: 283.4079
Monoisotopic: 283.193614427
Chemical FormulaC19H25NO
InChI KeyInChIKey=OZYUPQUCAUTOBP-QXAKKESOSA-N
InChI
InChI=1S/C19H25NO/c1-2-10-20-11-9-19-8-4-3-5-16(19)18(20)12-14-6-7-15(21)13-17(14)19/h2,6-7,13,16,18,21H,1,3-5,8-12H2/t16-,18+,19+/m0/s1
IUPAC Name
(1R,9R,10R)-17-(prop-2-en-1-yl)-17-azatetracyclo[7.5.3.0¹,¹⁰.0²,⁷]heptadeca-2(7),3,5-trien-4-ol
SMILES
[H][C@@]12CCCC[C@@]11CCN(CC=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 complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids.
PharmacodynamicsLevallorphan, an opioid antagonist similar to naloxone, is used to treat drug overdoses. Levallorphan differs from naloxone in that it also possesses some agonist properties. It is an analogue of levelorphanol that counteracts the actions of narcotic analgesics such as morphine. It is used especially in the treatment of respiratory depression due to narcotic overdoses. Levallorphan prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
Mechanism of actionLevallorphan antagonizes opioid effects by competing for the same receptor sites. It binds to the opioid mu receptor and the nicotinic acetylcholine receptor alpha2/alpha3.
Related Articles
AbsorptionRapidly absorbed.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life1 hour
ClearanceNot Available
ToxicityOral, rat LD50: 109±4 mg/kg
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Levallorphan Action PathwayDrug actionSMP00683
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9691
Blood Brain Barrier+0.9948
Caco-2 permeable+0.7313
P-glycoprotein substrateSubstrate0.7698
P-glycoprotein inhibitor IInhibitor0.6659
P-glycoprotein inhibitor IIInhibitor0.6439
Renal organic cation transporterInhibitor0.7978
CYP450 2C9 substrateNon-substrate0.8101
CYP450 2D6 substrateSubstrate0.5731
CYP450 3A4 substrateSubstrate0.5438
CYP450 1A2 substrateNon-inhibitor0.5676
CYP450 2C9 inhibitorNon-inhibitor0.8877
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.8743
CYP450 3A4 inhibitorNon-inhibitor0.8409
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5908
Ames testNon AMES toxic0.7723
CarcinogenicityNon-carcinogens0.9563
BiodegradationNot ready biodegradable0.9973
Rat acute toxicity2.5065 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6508
hERG inhibition (predictor II)Non-inhibitor0.5385
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point181 °CPhysProp
water solubility633 mg/LNot Available
logP3.48HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0252 mg/mLALOGPS
logP3.91ALOGPS
logP3.76ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)10.36ChemAxon
pKa (Strongest Basic)9.41ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity87.24 m3·mol-1ChemAxon
Polarizability32.68 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
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Methylnaltrexone is combined with Levallorphan.
NaloxegolThe risk or severity of adverse effects can be increased when Levallorphan is combined with Naloxegol.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
partial 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. Picker MJ, Benyas S, Horwitz JA, Thompson K, Mathewson C, Smith MA: Discriminative stimulus effects of butorphanol: influence of training dose on the substitution patterns produced by Mu, Kappa and Delta opioid agonists. J Pharmacol Exp Ther. 1996 Dec;279(3):1130-41. [PubMed:8968334 ]
  2. Traynor JR, Nahorski SR: Modulation by mu-opioid agonists of guanosine-5'-O-(3-[35S]thio)triphosphate binding to membranes from human neuroblastoma SH-SY5Y cells. Mol Pharmacol. 1995 Apr;47(4):848-54. [PubMed:7723747 ]
  3. Selley DE, Sim LJ, Xiao R, Liu Q, Childers SR: mu-Opioid receptor-stimulated guanosine-5'-O-(gamma-thio)-triphosphate binding in rat thalamus and cultured cell lines: signal transduction mechanisms underlying agonist efficacy. Mol Pharmacol. 1997 Jan;51(1):87-96. [PubMed:9016350 ]
  4. Emmerson PJ, Clark MJ, Mansour A, Akil H, Woods JH, Medzihradsky F: Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor. J Pharmacol Exp Ther. 1996 Sep;278(3):1121-7. [PubMed:8819494 ]
  5. Morgan D, Picker MJ: The mu opioid irreversible antagonist beta-funaltrexamine differentiates the discriminative stimulus effects of opioids with high and low efficacy at the mu opioid receptor. Psychopharmacology (Berl). 1998 Nov;140(1):20-8. [PubMed:9862398 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23