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

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H25NO3
Molecular Weight 339.4281
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NALMEFENE

SMILES

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

InChI

InChIKey=WJBLNOPPDWQMCH-MBPVOVBZSA-N
InChI=1S/C21H25NO3/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/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

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

1.36175039E12
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
The role of endogenous opioids in congestive heart failure: effects of nalmefene on systemic and regional hemodynamics in dogs.
1987 Feb
A panic attack precipitated by opiate blockade--a case study.
1987 Oct
Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications.
1998 Mar
New developments in the pharmacotherapy of alcohol dependence.
2001
Inverse agonists and neutral antagonists at mu opioid receptor (MOR): possible role of basal receptor signaling in narcotic dependence.
2001 Jun
The use of nalmefene for intrathecal opioid-associated nausea in postpartum patients.
2002 Feb
Comparison of the discriminative and neuroendocrine effects of centrally penetrating kappa-opioid agonists in rhesus monkeys.
2002 Oct
Characterization of scratching responses in rats following centrally administered morphine or bombesin.
2003 Nov
Pharmacotherapy of alcohol dependence: a review of the clinical data.
2004
A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence.
2004 Aug
Pharmacotherapy for erectile dysfunction.
2004 Sep
Unexpected placebo response in premenstrual dysphoric disorder: implication of endogenous opioids.
2005 Oct
Comorbidity issues in the pharmacological treatment of Pathological Gambling: a critical review.
2005 Oct 10
Acamprosate: a new tool in the battle against alcohol dependence.
2006 Dec
Epidemiologic and clinical updates on impulse control disorders: a critical review.
2006 Dec
Pharmacoprophylaxis of alcohol dependence: Review and update Part I: Pharmacology.
2007 Jan
Targeted nalmefene with simple medical management in the treatment of heavy drinkers: a randomized double-blind placebo-controlled multicenter study.
2007 Jul
Emerging pharmacologic options for treating postoperative ileus.
2007 Oct 15
Pharmacological evidence for a motivational role of kappa-opioid systems in ethanol dependence.
2008 Feb
[Pharmacokinetics of nalmefene after a single or multiple intravenous doses in Chinese healthy volunteers].
2008 Oct
Pathological gambling and compulsive buying: do they fall within an obsessive-compulsive spectrum?
2010
Opioid antagonists for alcohol dependence.
2010 Dec 8
Opioid antagonists under heavy sedation or anaesthesia for opioid withdrawal.
2010 Jan 20
[Serum NT-proBNP levels in neonates with severe asphyxia and the effects of nalmefene on the NT-proBNP levels].
2010 Nov
Antipruritic treatment with systemic μ-opioid receptor antagonists: a review.
2010 Oct
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 17:44:24 UTC 2023
Edited
by admin
on Sat Dec 16 17:44:24 UTC 2023
Record UNII
TOV02TDP9I
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NALMEFENE
HSDB   INN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
NALMEFENE [USAN]
Common Name English
17-(Cyclopropylmethyl)-4,5α-epoxy-6-methylenemorphinan-3,14-diol
Systematic Name English
SRD-174
Code English
ORF-11676
Code English
NALMEFENE [HSDB]
Common Name English
Nalmefene [WHO-DD]
Common Name English
ORF 11676
Code English
ORF 1167
Code English
JKB-121
Code English
JF-1
Code English
NALMEFENE [MI]
Common Name English
nalmefene [INN]
Common Name English
ORF-1167
Code English
MORPHINAN-3,14-DIOL, 17-(CYCLOPROPYLMETHYL)-4,5-EPOXY-6-METHYLENE-, (5.ALPHA.)-
Systematic Name English
NALMEFENE [VANDF]
Common Name English
SRD174
Code English
NALMEFENE [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C681
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
NDF-RT N0000000154
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
WHO-VATC QN07BB05
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
WHO-ATC N07BB05
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
NDF-RT N0000175691
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
LIVERTOX NBK548295
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
Code System Code Type Description
MESH
C038981
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
INN
5189
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
EVMPD
SUB09139MIG
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
WIKIPEDIA
NALMEFENE
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
NCI_THESAURUS
C61855
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
USAN
T-2
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
IUPHAR
1628
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
FDA UNII
TOV02TDP9I
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
ChEMBL
CHEMBL982
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
DAILYMED
TOV02TDP9I
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
DRUG CENTRAL
1876
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
CAS
55096-26-9
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
DRUG BANK
DB06230
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
EPA CompTox
DTXSID8023347
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
PUBCHEM
5284594
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
HSDB
6761
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
SMS_ID
100000084441
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY
RXCUI
31479
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY RxNorm
MERCK INDEX
m7715
Created by admin on Sat Dec 16 17:44:25 UTC 2023 , Edited by admin on Sat Dec 16 17:44:25 UTC 2023
PRIMARY Merck Index
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Related Record Type Details
METABOLITE INACTIVE -> PARENT
MAJOR
URINE
METABOLITE ACTIVE -> PARENT
MINOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC