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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H25NO3.ClH
Molecular Weight 375.889
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALMEFENE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=GYWMRGWFQPSQLK-OPHZJPRHSA-N
InChI=1S/C21H25NO3.ClH/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/t16-,19+,20+,21-;/m1./s1

HIDE SMILES / InChI

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

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

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
New developments in the pharmacotherapy of alcohol dependence.
2001
The impact of nalmefene on side effects due to intrathecal morphine at cesarean section.
2001 Jun
Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.
2001 Jun
Pharmacological control of opioid-induced pruritus: a quantitative systematic review of randomized trials.
2001 Jun
Nalmefene for elective reversal of procedural sedation in children.
2001 Nov
Preclinical models to evaluate potential pharmacotherapeutic agents in treating alcoholism and studying the neuropharmacological bases of ethanol-seeking behaviors in rats.
2002 Aug
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
Characterization of scratching responses in rats following centrally administered morphine or bombesin.
2003 Nov
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
Determination of nalmefene by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
2005 Apr
Opioid antagonists for alcohol dependence.
2005 Jan 25
Unexpected placebo response in premenstrual dysphoric disorder: implication of endogenous opioids.
2005 Oct
Phobic memory and somatic vulnerabilities in anorexia nervosa: a necessary unity?
2005 Sep 6
Acamprosate: a new tool in the battle against alcohol dependence.
2006 Dec
The permeation of nalmefene hydrochloride across different regions of ovine nasal mucosa.
2006 Dec
Optimization of the preparation of nalmefene-loaded sustained-release microspheres using central composite design.
2006 Jul
Pharmacologic treatments for opioid dependence: detoxification and maintenance options.
2007
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
Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study.
2007 Jul
Application of a sensitive liquid chromatographic/tandem mass spectrometric method to pharmacokinetic study of nalmefene in humans.
2007 Jun 1
Plasma met-enkephalin, beta-endorphin and leu-enkephalin levels in human hepatic encephalopathy.
2007 Mar-Apr
Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food.
2008 Feb
Imaging of opioid receptors in the central nervous system.
2008 May
Cholestatic hepatitis as a possible new side-effect of oxycodone: a case report.
2008 May 1
Primary biliary cirrhosis.
2009 Sep
Pediatric sedation: a global challenge.
2010
Pharmacogenetics: a tool for identifying genetic factors in drug dependence and response to treatment.
2010 Dec
Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
2010 Jan 20
Antipruritic treatment with systemic μ-opioid receptor antagonists: a review.
2010 Oct
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 Fri Dec 15 15:48:05 GMT 2023
Edited
by admin
on Fri Dec 15 15:48:05 GMT 2023
Record UNII
K7K69QC05X
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALMEFENE HYDROCHLORIDE
MART.   MI   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
Nalmefene hydrochloride [WHO-DD]
Common Name English
JF-1 HYDROCHLORIDE
Code English
NALMEFENE HYDROCHLORIDE [VANDF]
Common Name English
NALMEFENE HCL
Common Name English
OPVEE
Brand Name English
NALMEFENE HYDROCHLORIDE [MART.]
Common Name English
17-CYCLOPROPYLMETHYL-4,5A-EPOXY-6-METHYLENEMORPHINAN-3,14-DIOL HYDROCHLORIDE
Common Name English
NALMEFENE HYDROCHLORIDE [MI]
Common Name English
NALMEFENE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
REVEX
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C681
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
Code System Code Type Description
RXCUI
236069
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY RxNorm
SMS_ID
100000076270
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
DAILYMED
K7K69QC05X
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
ChEMBL
CHEMBL982
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
FDA UNII
K7K69QC05X
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
EVMPD
SUB14628MIG
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
NCI_THESAURUS
C47631
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
CAS
58895-64-0
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
MERCK INDEX
m7715
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY Merck Index
DRUG BANK
DBSALT001446
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
PUBCHEM
5388881
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
EPA CompTox
DTXSID70891705
Created by admin on Fri Dec 15 15:48:05 GMT 2023 , Edited by admin on Fri Dec 15 15:48:05 GMT 2023
PRIMARY
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PARENT -> SALT/SOLVATE
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