U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H25NO3.ClH.2H2O
Molecular Weight 411.92
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALMEFENE HYDROCHLORIDE DIHYDRATE

SMILES

O.O.Cl.[H][C@@]12OC3=C4C(C[C@H]5N(CC6CC6)CC[C@@]14[C@@]5(O)CCC2=C)=CC=C3O

InChI

InChIKey=XOBQQQVDLSMXCE-JVRGSUDVSA-N
InChI=1S/C21H25NO3.ClH.2H2O/c1-12-6-7-21(24)16-10-14-4-5-15(23)18-17(14)20(21,19(12)25-18)8-9-22(16)11-13-2-3-13;;;/h4-5,13,16,19,23-24H,1-3,6-11H2;1H;2*1H2/t16-,19+,20+,21-;;;/m1.../s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C21H25NO3
Molecular Weight 339.4281
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Nalmefene is the first medication approved for alcoholism with the primary goal of reducing alcohol intake in an as needed approach. Nalmefene received a marketing authorization valid throughout the European Union on February 25, 2013 and is under development in Asia. Nalmefene is an opioid system modulator with a distinct μ, δ, and κ receptor profile. In vitro studies have demonstrated that Nalmefene is a selective opioid receptor ligand with antagonist activity at the μ and δ receptors and partial agonist activity at the κ receptor. In vivo studies have demonstrated that nalmefene reduces alcohol consumption, possibly by modulating cortico-mesolimbic functions. In the US, immediate-release injectable nalmefene was approved in 1995 as an antidote for opioid overdose. It was sold under the trade name Revex. The product was discontinued by its manufacturer around 2008. Currently Nalmefene is sold under the trade name Selincro. Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking-risk level, without physical withdrawal symptoms and who do not require immediate detoxification.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Selincro

Approved Use

Selincro is indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking-risk level, without physical withdrawal symptoms and who do not require immediate detoxification.

Launch Date

2013
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
155 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
177 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
24.3 ng/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
57.9 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
109 ng × h/mL
6 mg single, intravenous
dose: 6 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1320 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
16.6 ng × h/mL
1 mg single, intravenous
dose: 1 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
16.9 ng × h/mL
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1876 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
191 ng × h/mL
12 mg single, intravenous
dose: 12 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
274 ng × h/mL
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
29.4 ng × h/mL
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
314 ng × h/mL
20 mg 2 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
385 ng × h/mL
24 mg single, intravenous
dose: 24 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
647 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.2 h
6 mg single, intravenous
dose: 6 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.8 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
10.8 h
1 mg single, intravenous
dose: 1 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
11.7 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.6 h
12 mg single, intravenous
dose: 12 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
10.3 h
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.4 h
2 mg single, intravenous
dose: 2 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
9.1 h
20 mg 2 times / day steady-state, oral
dose: 20 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8.9 h
24 mg single, intravenous
dose: 24 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.4 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NALMEFENE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
18 mg 1 times / day steady, oral
Recommended
Dose: 18 mg, 1 times / day
Route: oral
Route: steady
Dose: 18 mg, 1 times / day
Sources:
unhealthy, 39 years
n = 1
Health Status: unhealthy
Condition: alcohol dependence and Schizoaffective Disorder
Age Group: 39 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Psychiatric decompensation...
AEs leading to
discontinuation/dose reduction:
Psychiatric decompensation (1 patient)
Sources:
300 mg 1 times / day multiple, oral
Highest studied dose
Dose: 300 mg, 1 times / day
Route: oral
Route: multiple
Dose: 300 mg, 1 times / day
Sources:
healthy, adult
n = 4
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 4
Sources:
300 mg single, oral
Highest studied dose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Sources:
healthy, adult
n = 4
Health Status: healthy
Age Group: adult
Sex: M
Population Size: 4
Sources:
0.75 ug/kg single, intravenous
Highest studied dose
Dose: 0.75 ug/kg
Route: intravenous
Route: single
Dose: 0.75 ug/kg
Sources:
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: postoperative pain
Age Group: adult
Sex: M+F
Population Size: 3
Sources:
DLT: Anesthesia reversal...
Dose limiting toxicities:
Anesthesia reversal (2 patients)
Sources:
0.5 ug/kg single, intravenous
MTD
Dose: 0.5 ug/kg
Route: intravenous
Route: single
Dose: 0.5 ug/kg
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: postoperative pain
Age Group: adult
Sex: M+F
Population Size: 18
Sources:
DLT: Anesthesia reversal...
Dose limiting toxicities:
Anesthesia reversal (3 patients)
Sources:
20 mg 2 times / day steady, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: alcohol dependence
Age Group: adult
Sex: M+F
Population Size: 7
Sources:
Disc. AE: Dizziness...
AEs leading to
discontinuation/dose reduction:
Dizziness (1 patient)
Sources:
5 mg 2 times / day steady, oral
Studied dose
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: alcohol dependence
Age Group: adult
Sex: M+F
Population Size: 7
Sources:
Disc. AE: Dizziness, Rash...
AEs leading to
discontinuation/dose reduction:
Dizziness (1 patient)
Rash (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Psychiatric decompensation 1 patient
Disc. AE
18 mg 1 times / day steady, oral
Recommended
Dose: 18 mg, 1 times / day
Route: oral
Route: steady
Dose: 18 mg, 1 times / day
Sources:
unhealthy, 39 years
n = 1
Health Status: unhealthy
Condition: alcohol dependence and Schizoaffective Disorder
Age Group: 39 years
Sex: M
Population Size: 1
Sources:
Anesthesia reversal 2 patients
DLT
0.75 ug/kg single, intravenous
Highest studied dose
Dose: 0.75 ug/kg
Route: intravenous
Route: single
Dose: 0.75 ug/kg
Sources:
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: postoperative pain
Age Group: adult
Sex: M+F
Population Size: 3
Sources:
Anesthesia reversal 3 patients
DLT
0.5 ug/kg single, intravenous
MTD
Dose: 0.5 ug/kg
Route: intravenous
Route: single
Dose: 0.5 ug/kg
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: postoperative pain
Age Group: adult
Sex: M+F
Population Size: 18
Sources:
Dizziness 1 patient
Disc. AE
20 mg 2 times / day steady, oral
Recommended
Dose: 20 mg, 2 times / day
Route: oral
Route: steady
Dose: 20 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: alcohol dependence
Age Group: adult
Sex: M+F
Population Size: 7
Sources:
Dizziness 1 patient
Disc. AE
5 mg 2 times / day steady, oral
Studied dose
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: alcohol dependence
Age Group: adult
Sex: M+F
Population Size: 7
Sources:
Rash 1 patient
Disc. AE
5 mg 2 times / day steady, oral
Studied dose
Dose: 5 mg, 2 times / day
Route: oral
Route: steady
Dose: 5 mg, 2 times / day
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: alcohol dependence
Age Group: adult
Sex: M+F
Population Size: 7
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
minor
minor
no
no
no
no
no
no
yes
yes
yes
Tox targets
PubMed

PubMed

TitleDatePubMed
Nalmefene: intravenous safety and kinetics of a new opioid antagonist.
1986 Jan
A panic attack precipitated by opiate blockade--a case study.
1987 Oct
A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCl for alcohol dependence.
1994 Oct
Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
1998 Mar
Dynorphin A1-13 causes elevation of serum levels of prolactin through an opioid receptor mechanism in humans: gender differences and implications for modulation of dopaminergic tone in the treatment of addictions.
1999 Jan
Preclinical models to evaluate potential pharmacotherapeutic agents in treating alcoholism and studying the neuropharmacological bases of ethanol-seeking behaviors in rats.
2002 Aug
Potentiation of the excitatory action of NMDA in ventrolateral periaqueductal gray by the mu-opioid receptor agonist, DAMGO.
2002 May 10
Comparison of the discriminative and neuroendocrine effects of centrally penetrating kappa-opioid agonists in rhesus monkeys.
2002 Oct
A clinical laboratory paradigm for evaluating medication effects on alcohol consumption: naltrexone and nalmefene.
2003 Apr
[Pathogenesis and treatment of pruritus in patients with cholestasis].
2003 Mar
Central opioid receptors differentially regulate the nalmefene-induced suppression of ethanol- and saccharin-reinforced behaviors in alcohol-preferring (P) rats.
2004 Feb
Pharmacotherapy for erectile dysfunction.
2004 Sep
Implantable technology for long-term delivery of nalmefene for treatment of alcoholism.
2004 Sep 28
Stimulation of the hypothalamic-pituitary-adrenal axis with the opioid antagonist nalmefene.
2005
Determination of nalmefene by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
2005 Apr
Comorbidity issues in the pharmacological treatment of Pathological Gambling: a critical review.
2005 Oct 10
Phobic memory and somatic vulnerabilities in anorexia nervosa: a necessary unity?
2005 Sep 6
The permeation of nalmefene hydrochloride across different regions of ovine nasal mucosa.
2006 Dec
Epidemiologic and clinical updates on impulse control disorders: a critical review.
2006 Dec
Multicenter investigation of the opioid antagonist nalmefene in the treatment of pathological gambling.
2006 Feb
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.
2007
Pharmacoprophylaxis of alcohol dependence: Review and update Part I: Pharmacology.
2007 Jan
Effects of salvinorin A, a kappa-opioid hallucinogen, on a neuroendocrine biomarker assay in nonhuman primates with high kappa-receptor homology to humans.
2007 Jan
Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.
2007 Mar-Apr
Evidence of accelerated ageing in clinical drug addiction from immune, hepatic and metabolic biomarkers.
2007 Sep 24
Methylnaltrexone in the treatment of opioid-induced constipation.
2008
Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report.
2008 May 1
Opioid antagonists for pharmacological treatment of alcohol dependence - a critical review.
2008 Nov
Predicting response to opiate antagonists and placebo in the treatment of pathological gambling.
2008 Nov
Agenda for specialty section in addiction medicine.
2008 Oct
[Pharmacokinetics of nalmefene after a single or multiple intravenous doses in Chinese healthy volunteers].
2008 Oct
The effects of herkinorin, the first mu-selective ligand from a salvinorin A-derived scaffold, in a neuroendocrine biomarker assay in nonhuman primates.
2008 Oct
Primary biliary cirrhosis.
2009 Sep
The Effects of Naltrexone Among Alcohol Non-Abstainers: Results from the COMBINE Study.
2010
Pediatric sedation: a global challenge.
2010
Pathological gambling and compulsive buying: do they fall within an obsessive-compulsive spectrum?
2010
In vivo characterization of the opioid antagonist nalmefene in mice.
2010 Apr 10
Human exposures to immobilising agents: results of an online survey.
2010 Aug 28
Pharmacogenetics: a tool for identifying genetic factors in drug dependence and response to treatment.
2010 Dec
Emerging drugs to treat alcoholism.
2010 Dec
Opioid antagonists for alcohol dependence.
2010 Dec 8
Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
2010 Jan 20
[Clinical observation of the effect of nalmefene in treatment of septic shock].
2010 Jun
[Serum NT-proBNP levels in neonates with severe asphyxia and the effects of nalmefene on the NT-proBNP levels].
2010 Nov
Nalmefene for treatment of alcohol dependence.
2010 Nov
Nalmefene in the treatment of pathological gambling: multicentre, double-blind, placebo-controlled study.
2010 Oct
Brain imaging studies in pathological gambling.
2010 Oct
Antipruritic treatment with systemic μ-opioid receptor antagonists: a review.
2010 Oct
Tailoring therapeutic strategies for treating posttraumatic stress disorder symptom clusters.
2010 Sep 7
Treatment of Gambling Disorders.
2014 Jun 1
Patents

Sample Use Guides

How much to take - The recommended dose is one tablet on days when you think there is a risk you will drink alcohol - The maximum dose is one tablet per day. How and when to take - You should take the tablet 1-2 hours before you start drinking alcohol. - Swallow the tablet whole, do not crush or divide the tablet. - You can take Selincro (Nalmefene) with or without food. Each film-coated tablet contains 18.06 mg nalmefene (as hydrochloride dihydrate).
Route of Administration: Oral
In Vitro Use Guide
Nalmefene antagonized the bindings of [3H]-dihydromorphine, [3H]-ethylketocyclazocine and [3H]-D-ala-D-leu enkephalin with IC50's in the low nanomolar range in rat brain membranes.. At the central mu receptor, nalmefene bound with an IC50 of 1.0 nM
Substance Class Chemical
Created
by admin
on Sat Dec 16 06:19:39 GMT 2023
Edited
by admin
on Sat Dec 16 06:19:39 GMT 2023
Record UNII
52Z0G7QVJX
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALMEFENE HYDROCHLORIDE DIHYDRATE
WHO-DD  
Common Name English
SELINCRO
Brand Name English
NALMEFENE HYDROCHLORIDE HYDRATE [JAN]
Common Name English
MORPHINAN-3,14-DIOL, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-6-METHYLENE-, HYDROCHLORIDE, HYDRATE (1:1:2), (5.ALPHA.)-
Common Name English
Nalmefene hydrochloride dihydrate [WHO-DD]
Common Name English
Classification Tree Code System Code
EMA ASSESSMENT REPORTS SELINCRO (AUTHORIZED: ALCOHOL-RELATED DISORDERS)
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
Code System Code Type Description
SMS_ID
100000156016
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
CAS
1228646-70-5
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
PUBCHEM
46209574
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
EPA CompTox
DTXSID50153757
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
DRUG BANK
DBSALT002636
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
FDA UNII
52Z0G7QVJX
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
EVMPD
SUB130094
Created by admin on Sat Dec 16 06:19:39 GMT 2023 , Edited by admin on Sat Dec 16 06:19:39 GMT 2023
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY