General
Preferred name
nalmefene
Synonyms
NALMEFENE HYDROCHLORIDE ()
Nalmefene HCl ()
JF-1 HYDROCHLORIDE ()
Revex ()
Nalmefene hydrochloride dihydrate ()
ORF 1167 ()
SRD-174 ()
JF-1 ()
ORF 11676 ()
Selincro ()
ORF-11676 ()
SRD174 ()
Nalmefene hydrochloride hydrate ()
Nalmetrene ()
ORF-1167 ()
JKB-121 ()
P&D ID
PD013331
CAS
58895-64-0
55096-26-9
1228646-70-5
Tags
drug
natural product
biased GPCR ligand
available
Approved by
PMDA
FDA
First approval
1995
Drug Status
investigational
approved
withdrawn
Drug indication
Antagonist (to narcotics)
Opioid dependence
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
Nalmefene has not been shown to produce tolerance, physical dependence, or abuse potential [L1024, FDA Label]. ; ; When adminsitered as an antidote for opioid overdose, nalmefene is not known to produce any respiratory depression, psychomimetic effects, or pupillary constriction [FDA Label]. In the absence of opioid agonists, there was no observable pharmacological activity. Nalmefene injection can produce acute withdrawal symptoms in individuals who are opioid-dependent.
INDICATION
Indicated for the reduction of alcohol consumption in adult patients with alcohol dependence who have a high drinking risk level (DRL), without physical withdrawal symptoms and who do not require immediate detoxification [L1024].; ; Indicated for the complete or partial reversal of opioid drug effects, including respiratory depression - induced by either natural or synthetic opioids - or in the management of known or suspected opioid overdose [FDA Label].
DESCRIPTION
Nalmefene is an opioid receptor antagonist.
(GtoPdb)
ABSORPTION
Following a single oral administration of 18.06 mg, nalmefene is rapidly absorbed with a peak plasma concentration (Cmax) of 16.5 ng/ml with the time to reach the peak concentration (Tmax) of approxmately 1.5 hours and the exposure (AUC) of 131 ng x h/ml. Although there is little association to clinical relevance, the AUC and Cmax values are expected to increase by 30 to 50%, respectively, and the Tmax is delayed by 30 minutes after consumption of high-fat food. The absolute oral bioavailability of nalmefene is 41% [L1024]. ; ; Nalmefene exhibits dose-proportional pharmacokinetics following intravenous injection. The Tmax following intramuscular or subcutaneous injection is approximately 1.5-2.3 hours. In an emergency setting, however, therapeutic plasma concentrations are likely to be reached within 5-15 minutes after a 1 mg dose given intravenously where the plasma concentration is approximately 3.7 ng/mL at 5 minutes in young adult males [FDA Label].
MOA
Nalmefene is an opioid system modulator with a distinct μ, δ, and κ receptor profile. It acts as a selective opioid receptor ligand with antagonist activity at the μ and δ receptors and partial agonist activity at the κ receptor [L1024, A31301]. Animal studies suggest that the kappa receptor signalling responses lead to antagonism of acute reward and positive reinforcement effects of drugs by decreasing dopamine in the nucleus accumbens [A31301]. Thus it is suggested that nalmefene may be more effective treatment for alcohol dependence than [DB00704], which is a pure mu and delta receptor antagonist [A31301]. In vivo studies and rat studies have demonstrated that nalmefene reduces self-administration of alcohol, possibly by modulating cortico-mesolimbic functions [L1024]. ; ; Nalmefene, a 6-methylene analogue of naltrexone, is a competitive opioid antagonist which binds with high affinity to the mu opioid receptor. Nalmefene itself does not induce any opioid activity, but prevents or reverses the effects of opioids such as respiratory depression and sedation when injected[FDA Label]. Some pharmacodynamic studies showed that nalmefene has a longer duration of action than naloxone at fully reversing doses [FDA Label] however the relative potency of these two antagonists are reported to be similar [A31302].
DESCRIPTION
Group I mGlu antagonist
(Tocris Bioactive Compound Library)
DESCRIPTION
Opioid receptor antagonist
(Tocriscreen Plus)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
28
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BiasDB
ChEMBL Approved Drugs
ChEMBL Drugs
Concise Guide to Pharmacology 2017/18
Concise Guide to Pharmacology 2019/20
Concise Guide to Pharmacology 2021/22
Concise Guide to Pharmacology 2023/24
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Other bioactive compounds
Prestwick Chemical Library
ReFrame library
TargetMol Bioactive Compound Library
Tocris Bioactive Compound Library
Tocriscreen Plus
Withdrawn 2.0
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
55
Molecular Weight
339.18
Hydrogen Bond Acceptors
4
Hydrogen Bond Donors
2
Rotatable Bonds
2
Ring Count
6
Aromatic Ring Count
1
cLogP
2.51
TPSA
52.93
Fraction CSP3
0.62
Chiral centers
4.0
Largest ring
6.0
QED
0.81
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
7-TM Receptors
Pathway
Endocrinology/Hormones
GPCR/G protein
Neuroscience
Target
Opioid Receptor
OPRD1, OPRK1, OPRM1
Opioid antagonist
Primary Target
Miscellaneous Opioids
MOA
Antagonist
kappa-Opioid Antagonists
Opioid Receptor antagonist
Member status
member
Indication
respiratory depression
ATC
N07BB05
Therapeutic Class
Anticraving Agents
Source data
