Identification

Name
Levallorphan
Accession Number
DB00504  (APRD00733)
Type
Small Molecule
Groups
Approved
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
Synonyms
  • Levallofano
  • Levallorphan
  • Lévallorphane
  • Levallorphanum
  • Levalorfano
External IDs
HSDB 2148 / Ro-1-7700
Product Ingredients
IngredientUNIICASInChI Key
Levallorphan TartrateU0VSF7HTN071-82-9FWMLYVACGDQRFU-ZTMWJVNESA-N
International/Other Brands
Lorfan (Takeda)
Categories
UNII
353613BU4U
CAS number
152-02-3
Weight
Average: 283.4079
Monoisotopic: 283.193614427
Chemical Formula
C19H25NO
InChI Key
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

Pharmacology

Indication

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

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.

TargetActionsOrganism
AMu-type opioid receptor
partial agonist
Human
Absorption

Rapidly absorbed.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic.

Route of elimination
Not Available
Half life

1 hour

Clearance
Not Available
Toxicity

Oral, rat LD50: 109±4 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Levallorphan Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AlfentanilThe therapeutic efficacy of Alfentanil can be decreased when used in combination with Levallorphan.
AlphacetylmethadolThe therapeutic efficacy of Alphacetylmethadol can be decreased when used in combination with Levallorphan.
AlphaprodineThe therapeutic efficacy of Alphaprodine can be decreased when used in combination with Levallorphan.
BezitramideThe therapeutic efficacy of Bezitramide can be decreased when used in combination with Levallorphan.
BuprenorphineThe therapeutic efficacy of Buprenorphine can be decreased when used in combination with Levallorphan.
ButorphanolThe therapeutic efficacy of Butorphanol can be decreased when used in combination with Levallorphan.
CarfentanilThe therapeutic efficacy of Carfentanil can be decreased when used in combination with Levallorphan.
CodeineThe therapeutic efficacy of Codeine can be decreased when used in combination with Levallorphan.
DextromoramideThe therapeutic efficacy of Dextromoramide can be decreased when used in combination with Levallorphan.
DextropropoxypheneThe therapeutic efficacy of Dextropropoxyphene can be decreased when used in combination with Levallorphan.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014647
KEGG Compound
C07069
PubChem Compound
5359371
PubChem Substance
46505682
ChemSpider
10481920
BindingDB
50326673
ChEBI
6431
ChEMBL
CHEMBL1254682
Therapeutic Targets Database
DAP000348
PharmGKB
PA164749284
Wikipedia
Levallorphan

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Hoffmann la roche inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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: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...
Gene Name
OPRM1
Uniprot ID
P35372
Uniprot Name
Mu-type opioid receptor
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 November 02, 2018 08:45