DrugBank: Levallorphan (DB00504)

targets (1)

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

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Brand names

Levallofano [Dcit]
Levallorphane [INN-French]
Levallorphanum [INN-Latin]
Levalorfano [INN-Spanish]
Lorfan
Naloxiphan

Brand name mixtures

Not Available

Categories

Analgesic Antagonists
Morphine Antidotes
Antinarcotic Agents
Narcotic Antagonists

CAS number

152-02-3

Weight

Average: 283.4079
Monoisotopic: 283.193614427

Chemical Formula

C₁₉H₂₅NO

InChI Key

InChIKey=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

Plain Text

IUPAC Name

(1R,9R,10R)-17-(prop-2-en-1-yl)-17-azatetracyclo[7.5.3.0^{1,10}.0^{2,7}]heptadeca-2(7),3,5-trien-4-ol

SMILES

[H][C@@]12CCCC[C@@]11CCN(CC=C)[C@@H]2CC2=C1C=C(O)C=C2

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Morphinans
Benzylisoquinolines

Substructures

Morphinans
Hydroxy Compounds
Alkanes and Alkenes
Naphthalenes
Phenols and Derivatives
Benzylisoquinolines
Benzene and Derivatives
Phenylpiperidines
Aliphatic and Aryl Amines
Phenanthrenes
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Phenylpropylamines
(Iso)quinolines and Derivatives
Cyclohexenes and Derivatives
Phenyl Esters
Amphetamines
Piperidines

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.

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

Not Available

Pharmacoeconomics

Manufacturers

Hoffmann la roche inc

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Melting point

181 oC

Experimental Properties

Property	Value	Source
water solubility	633 mg/L	PhysProp
logP	3.9	PhysProp

Predicted Properties

Property	Value	Source
water solubility	2.52e-02 g/l	ALOGPS
logP	3.91	ALOGPS
logP	3.75	ChemAxon Molconvert
logS	-4.05	ALOGPS
pKa		ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	23.47	ChemAxon Molconvert
rotatable bond count	2	ChemAxon Molconvert
refractivity	87.24	ChemAxon Molconvert
polarizability	32.68	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Compound	C07069
PubChem Compound	5359371
PubChem Substance	46505682
ChemSpider	4514267
Therapeutic Targets Database	DAP000348
Drug Product Database	0

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction

Food Interactions

Not Available

Targets
1. Mu-type opioid receptor Pharmacological action: yes Actions: partial agonist Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin Organism class: human UniProt ID: P35372 Gene: OPRM1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report 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 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 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 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 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

Targets

1. Mu-type opioid receptor

Pharmacological action: yes
Actions: partial agonist

Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Receptor for beta-endorphin

Organism class: human
UniProt ID: P35372 Link_out

Gene: OPRM1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
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
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
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
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

Comments

Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:40

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