LEVORPHANOL

First approved in 1953

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H23NO
Molecular Weight	257.3706
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CCCC[C@@]13CCN(C)[C@@H]2CC4=C3C=C(O)C=C4

InChI

InChIKey=JAQUASYNZVUNQP-USXIJHARSA-N

InChI=1S/C17H23NO/c1-18-9-8-17-7-3-2-4-14(17)16(18)10-12-5-6-13(19)11-15(12)17/h5-6,11,14,16,19H,2-4,7-10H2,1H3/t14-,16+,17+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.drugs.com/pro/levorphanol.html | https://www.ncbi.nlm.nih.gov/pubmed/17039381

Levorphanol, brand name Levo-Dromoran, is an opioid medication used to treat moderate to severe pain. Levorphanol is indicated for the management of moderate to severe pain where an opioid analgesic is appropriate. It is a potent synthetic opioid mu-receptor agonist similar in action to morphine. Like other opioid mu-receptor agonists, it is believed to act at receptors in both the brain and spinal cord to alter the transmission and perception of pain. The onset and peak analgesic effects following administration of levorphanol are similar to morphine when administered at equal analgesic doses. Levorphanol produces a degree of respiratory depression similar to that produced by morphine at equal analgesic doses, and like many opioid mu-receptor agonists, levorphanol produces euphoria or has a positive effect on mood in many individuals.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Mu opioid receptor 221 Target ID: CHEMBL233 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17039381 \| https://www.ncbi.nlm.nih.gov/pubmed/17276685	Agonist 2678	0.21 nM [Ki]
Delta opioid receptor 77 Target ID: CHEMBL236 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17039381	Agonist 2678	4.2 nM [Ki]
Kappa opioid receptor 108 Target ID: CHEMBL237 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17039381	Agonist 2678	2.3 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Pain 614 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/074278.PDF	Palliative		Approved 8429	Levorphanol Tartrate Approved Use Levorphanol Tartrate Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Launch Date 1953

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587		substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19797609/	yes [IC50 11.5 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19797609/	yes [IC50 >50 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19797609/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19797609/	yes

Sourcing

Vendor/Aggregator	ID	URL
AAA Chemistry	AR-1E1926
ABI Chem	AC1L1H05
ABI Chem	AC1Q7AI1
AHH Chemical co.,ltd	MT-53063	http://www.ahhchemical.com/product/MT-53063.html
BOC Sciences	125-73-5	https://www.bocsci.com/dextromethorphan-ep-impurity-b-dextrorphan-cas-125-73-5-item-470048.html
BioChemPartner	BCP24334	http://www.biochempartner.com/125-73-5-BCP24334
Clearsynth	CS-O-16970	https://www.clearsynth.com/en/CSO16970.html
Compound Cloud	5359272
Compound Cloud	5462348
HongKong Chemhere	SCA54099
MuseChem	I014442
NovoSeek	3918
NovoSeek	5390113
Smolecule	S532999	http://www.smolecule.com/products/s532999
THE BioTek	bt-272670	https://www.thebiotek.com/product/inhibitors/bt-272670
Tetrahedron	TS81326
Toronto Research Chemicals	KIT8295
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-0703A
ZINC	ZINC000003812984	http://zinc15.docking.org/substances/ZINC000003812984
eMolecules	261267554
eMolecules	48858227

PubMed

Title	Date	PubMed
Comparison of opioid agonists in maintaining responding and in suppressing morphine withdrawal in rhesus monkeys.	1981	6794076
Prostaglandin hyperalgesia, V: a peripheral analgesic receptor for opiates.	1982 Jan	6278540
Relative cataleptic potency of narcotic analgesics, including 3,6-dibutanoylmorphine and 6-monoacetylmorphine.	1984	6543399
Differential effects of morphinan drugs on haloperidol-induced catalepsy in rats: a comparative study with an N-methyl-D-aspartate antagonist.	1991 Mar-Apr	1685312
Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception.	1995 Sep	7562497
Age-related differences in sensitivity to the antinociceptive effects of opioids in male rats. Influence of nociceptive intensity and intrinsic efficacy at the mu receptor.	2001 Aug	11498722
Clinical pharmacology of opioids for pain.	2002 Jul-Aug	12479250
Sex-related differences in mechanical nociception and antinociception produced by mu- and kappa-opioid receptor agonists in rats.	2002 Oct 4	12354566
Sensitivity to the effects of opioids in rats with free access to exercise wheels: mu-opioid tolerance and physical dependence.	2003 Aug	12709780
Discrimination of a single dose of morphine followed by naltrexone: substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence.	2003 Mar	12604679
Opioids and chronic neuropathic pain.	2003 Mar 27	12660393
Opioids ease neuropathic pain, but..	2003 May	12739461
Discriminative stimulus effects of acute morphine followed by naltrexone in the squirrel monkey.	2003 May	12644889
Differential regulation of the human kappa opioid receptor by agonists: etorphine and levorphanol reduced dynorphin A- and U50,488H-induced internalization and phosphorylation.	2003 May	12606694
The competitive N-methyl-D-aspartate receptor antagonist (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959) potentiates the antinociceptive effects of opioids that vary in efficacy at the mu-opioid receptor.	2003 Nov	12975489
[Fundamentals of modern treatment of myopia].	2005	16519089
Social and environmental influences on opioid sensitivity in rats: importance of an opioid's relative efficacy at the mu-receptor.	2005 Aug	15778888
Analgesic therapy in postherpetic neuralgia: a quantitative systematic review.	2005 Jul	16013891
Over-the-counter cold medications-postmortem findings in infants and the relationship to cause of death.	2005 Oct	16419411
Restless legs syndrome: diagnosis and review of management options.	2006 Jun	19412460
Opioid peptides and receptors in joint tissues: study in the rat.	2006 Jun	16649179
Chronic exercise decreases sensitivity to mu opioids in female rats: correlation with exercise output.	2006 Sep	16904173
Can levorphanol be used like methadone for intractable refractory pain?	2007 Apr	17472497
Levorphanol revisited.	2007 Dec	18095794
Does purity of supplements count?	2007 Jan	17208063
The effect of opiates on the activity of human placental aromatase/CYP19.	2007 Jan 15	17118343
Current aproach to cancer pain management: Availability and implications of different treatment options.	2007 Jun	18488078
Levorphanol: the forgotten opioid.	2007 Mar	17039381
High-affinity carbamate analogues of morphinan at opioid receptors.	2007 Mar 15	17276685
Morphine reduces local cytokine expression and neutrophil infiltration after incision.	2007 Oct 2	17908329
Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A.	2007 Oct 26	17897634
An evaluation of the genotoxicity of the antitussive drug Dextromethorphan.	2008 Apr	18160193
Effects of environmental enrichment on sensitivity to mu, kappa, and mixed-action opioids in female rats.	2008 Jul 5	18456292
Opioid pharmacology.	2008 Mar	18443637
A retrospective study on the impact of comorbid depression or anxiety on healthcare resource use and costs among diabetic neuropathy patients.	2009 Jun 30	19566952
Preoperative oral dextromethorphan does not reduce pain or morphine consumption after open cholecystectomy.	2010 Feb	20394254
Exploration of catalytic properties of CYP2D6 and CYP3A4 through metabolic studies of levorphanol and levallorphan.	2010 Jan	19797609
Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors.	2010 Jan 14	19928862

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Light Sedation Premedication for Anesthesia: 1 to 2 mg IM or subcutaneously, administered 60 to 90 minutes before surgery. Older or debilitated patients usually require less drug. Two mg of levorphanol is approximately equivalent to 10 to 15 mg of morphine or 100 mg of meperidine. Usual Adult Dose for Pain IV: 1 mg every 3 to 6 hours as needed. IM or subcutaneous: 1 to 2 mg every 6 to 8 hours as needed. Oral: 2 mg every 6 to 8 hours as needed. May be increased to 3 mg every 6 to 8 hours.

Route of Administration: Other

In Vitro Use Guide

Levorphanol (5-100 uM), consistently depressed the responses evoked by the putative inhibitory amino acid neurotransmitters glycine and beta-alanine but not GABA in cultured mouse spinal cord neurons.

Name

Type

Language

LEVORPHANOL

Official Name

English

Levorphanol [WHO-DD]

Common Name

English

LEVORPHANOL [HSDB]

Common Name

English

LEVORPHANOL [MI]

Common Name

English

RO 1-5431

Code

English

levorphanol [INN]

Common Name

English

IDS-NL-007

Code

English

LEVORPHANOL [VANDF]

Common Name

English

LEVORPHAN

Common Name

English

17-METHYLMORPHINAN-3-OL

Systematic Name

English

2H-10,4A-IMINOETHANOPHENANTHREN-6-OL, 1,3,4,9,10,10A-HEXAHYDRO-11-METHYL-

Systematic Name

English

(-)-3-HYDROXY-N-METHYLMORPHINAN

Systematic Name

English

N-METHYL-3-HYDROXYMORPHINAN

Systematic Name

English

AROMARONE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67413