IDPharmacologyInteractionsReferencesTrialsEconomicsPropertiesSpectraTaxonomy
Targets (1)
Targets (1)Biointeractions (1)

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Identification
NameLevallorphan
Accession NumberDB00504  (APRD00733)
TypeSmall Molecule
GroupsApproved
Description

An 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
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Levallofano
Levallorphan
Lévallorphane
Levallorphanum
Levalorfano
Lorfan
Naloxiphan
External IDs HSDB 2148 / Ro-1-7700 / UNII-U0VSF7HTN0
Product Ingredients
IngredientUNIICASInChI KeyDetails
Levallorphan TartrateU0VSF7HTN0 71-82-9FWMLYVACGDQRFU-ZTMWJVNESA-NDetails
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
Categories
UNII353613BU4U
CAS number152-02-3
WeightAverage: 283.4079
Monoisotopic: 283.193614427
Chemical FormulaC19H25NO
InChI KeyOZYUPQUCAUTOBP-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
Pharmacology
Indication

For the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids.

Structured Indications Not Available
Pharmacodynamics

Levallorphan, 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 action

Levallorphan antagonizes opioid effects by competing for the same receptor sites. It binds to the opioid mu receptor and the nicotinic acetylcholine receptor alpha2/alpha3.

TargetKindPharmacological actionActionsOrganismUniProt ID
Mu-type opioid receptorProteinyes
partial agonist
HumanP35372 details
Related Articles
Absorption

Rapidly absorbed.

Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half life

1 hour

ClearanceNot Available
Toxicity

Oral, rat LD50: 109±4 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Levallorphan Action PathwayDrug actionSMP00683
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
MethylnaltrexoneThe risk or severity of adverse effects can be increased when Methylnaltrexone is combined with Levallorphan.Approved
NaloxegolThe risk or severity of adverse effects can be increased when Levallorphan is combined with Naloxegol.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
Manufacturers
  • Hoffmann la roche inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)181 °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 RuleNoChemAxon
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 )
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
Taxonomy
DescriptionThis compound belongs to the class of chemical entities 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.
KingdomChemical entities
Super ClassOrganic compounds
ClassAlkaloids and derivatives
Sub ClassMorphinans
Direct ParentMorphinans
Alternative ParentsPhenanthrenes and derivatives / Benzazocines / Tetralins / Aralkylamines / 1-hydroxy-2-unsubstituted benzenoids / Piperidines / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds
SubstituentsMorphinan / Phenanthrene / Benzazocine / Tetralin / 1-hydroxy-2-unsubstituted benzenoid / Aralkylamine / Piperidine / Benzenoid / Tertiary aliphatic amine / Tertiary amine
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsmorphinane alkaloid (CHEBI:6431 )

Targets

Details
1. Mu-type opioid receptor
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 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:49