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

Similar Structures

Synonyms

Levallofano
Levallorphan
Lévallorphane
Levallorphanum
Levalorfano

External IDs

HSDB 2148 / Ro-1-7700

Product Ingredients

Ingredient	UNII	CAS	InChI Key
Levallorphan tartrate	U0VSF7HTN0	71-82-9	FWMLYVACGDQRFU-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.

Target	Actions	Organism
AMu-type opioid receptor	partial agonist	Humans

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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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

Pathway	Category
Levallorphan Action Pathway	Drug action

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

Drug	Interaction
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Alfentanil	The therapeutic efficacy of Alfentanil can be decreased when used in combination with Levallorphan.
Alphacetylmethadol	The therapeutic efficacy of Alphacetylmethadol can be decreased when used in combination with Levallorphan.
Alphaprodine	The therapeutic efficacy of Alphaprodine can be decreased when used in combination with Levallorphan.
Bezitramide	The therapeutic efficacy of Bezitramide can be decreased when used in combination with Levallorphan.
Buprenorphine	The therapeutic efficacy of Buprenorphine can be decreased when used in combination with Levallorphan.
Butorphanol	The therapeutic efficacy of Butorphanol can be decreased when used in combination with Levallorphan.
Carfentanil	The therapeutic efficacy of Carfentanil can be decreased when used in combination with Levallorphan.
Codeine	The therapeutic efficacy of Codeine can be decreased when used in combination with Levallorphan.
Dexketoprofen	The therapeutic efficacy of Dexketoprofen can be decreased when used in combination with Levallorphan.
Dextromoramide	The therapeutic efficacy of Dextromoramide can be decreased when used in combination with Levallorphan.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

Evidence Level

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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

Property	Value	Source
melting point (°C)	181 °C	PhysProp
water solubility	633 mg/L	Not Available
logP	3.48	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	0.0252 mg/mL	ALOGPS
logP	3.91	ALOGPS
logP	3.76	ChemAxon
logS	-4	ALOGPS
pKa (Strongest Acidic)	10.36	ChemAxon
pKa (Strongest Basic)	9.41	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	23.47 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	87.24 m³·mol^-1	ChemAxon
Polarizability	32.68 Å³	ChemAxon
Number of Rings	4	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	No	ChemAxon

Predicted ADMET features

Property	Value	Probability
Human Intestinal Absorption	+	0.9691
Blood Brain Barrier	+	0.9948
Caco-2 permeable	+	0.7313
P-glycoprotein substrate	Substrate	0.7698
P-glycoprotein inhibitor I	Inhibitor	0.6659
P-glycoprotein inhibitor II	Inhibitor	0.6439
Renal organic cation transporter	Inhibitor	0.7978
CYP450 2C9 substrate	Non-substrate	0.8101
CYP450 2D6 substrate	Substrate	0.5731
CYP450 3A4 substrate	Substrate	0.5438
CYP450 1A2 substrate	Non-inhibitor	0.5676
CYP450 2C9 inhibitor	Non-inhibitor	0.8877
CYP450 2D6 inhibitor	Inhibitor	0.8931
CYP450 2C19 inhibitor	Non-inhibitor	0.8743
CYP450 3A4 inhibitor	Non-inhibitor	0.8409
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.5908
Ames test	Non AMES toxic	0.7723
Carcinogenicity	Non-carcinogens	0.9563
Biodegradation	Not ready biodegradable	0.9973
Rat acute toxicity	2.5065 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Strong inhibitor	0.6508
hERG inhibition (predictor II)	Non-inhibitor	0.5385

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not 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 compoundsHydrocarbon derivatives
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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

Property	Measurement	pH	Temperature (°C)	References
Ki (nM)	0.48	N/A	N/A	21621410
Ki (nM)	1.29	N/A	N/A	21621410
Ki (nM)	1.69	N/A	N/A	21621410

Details1. Mu-type opioid receptor

Kind: Protein
Organism: Humans
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

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]
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]
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]
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]
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 April 03, 2019 09:41

Levallorphan

Identification

Structure for Levallorphan (DB00504)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Targets

References