General
Preferred name
MEMANTINE
Synonyms
MEMANTINE HYDROCHLORIDE ()
D-145 (hydrochloride) ()
Memantine HCl ()
Namenda ()
D-145 (hydrochloride)Memantine HCl ()
Memantine hydrochloride41100-52-1 ()
Akatinol ()
FP-01 ()
Memantine merz ()
Memary ()
Namenda Xr ()
Balaxur ()
Memantine accord ()
Auxura ()
Ebixa ()
Marixino ()
Memantine ratiopharm ()
Memantine mylan ()
NSC-102290 ()
Acrescent ()
Nemdatine ()
Memantine lek ()
Valios ()
SUN-Y7017 ()
NSC-757843 ()
Memantina ()
D-145 ()
DRG-0267 ()
Memantine ()
Memantine (hydrochloride) ()
Memantine-d6 (hydrochloride) ()
P&D ID
PD009581
CAS
41100-52-1
19982-08-2
1189713-18-5
Tags
available
drug
Approved by
EMA
FDA
First approval
2002
2003
Drug indication
Alzheimer disease
Drug Status
approved
investigational
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
MOA Continuous activation of the N-methyl-D-aspartate (NMDA) receptors in the central nervous system caused by _glutamate_ is thought to cause some of the Alzheimer's disease symptoms. This overactivation is thought to contribute to neurotoxicity due to the excitatory properties of glutamate [T556]. The pharmacological effect of memantine likely occurs via the drug's behavior as an uncompetitive (open-channel) NMDA receptor antagonist, preventing glutamate action on this receptor. Memantine has a preference for the NMDA receptor-operated cation channels. Despite these antagonist effects, memantine has not been proven to prevent or retard the neurodegeneration seen in patients diagnosed with Alzheimer’s disease [FDA label].
INDICATION Memantine is used to manage moderate to severe Alzheimer's dementia [FDA label]. ; ; A more recent systemic review and meta-analysis [A177106] indicates that memantine is beneficial as a first line drug for the treatment of Alzheimer's dementia. Cholinesterase inhibitors may be added to memantine for further beneficial effects on behavioral symptoms and other symptoms of dementia [A177106].
ROE This drug is mainly excreted in the urine. Approximately 48% of administered memantine is excreted unchanged in urine [FDA label]. ; ; The remainder of the drug is metabolized to three main metabolites. These metabolites are the N-glucuronide conjugate, 6-hydroxy memantine, and 1-nitroso-deaminated memantine, which show minimal NMDA receptor antagonist activity [FDA label]. ;
METABOLISM This drug is partially metabolized in the liver. The hepatic CYP450 enzyme system does not majorly contribute to the metabolism of this drug [FDA label].
ABSORPTION After an oral dose, memantine is well absorbed. Its peak drug concentrations are attained in about 3-7 hours. Memantine shows linear pharmacokinetics when given at normal therapeutic doses. This drug can be taken without regard to food, as there is no effect of food on memantine absorption [FDA label].
HALF-LIFE Within the range of 60-100 hours [FDA label].; ; The terminal elimination half-life was significantly increased in patients with moderate to severe renal impairment, in comparison with patients with normal renal function [FDA label]. Exercise caution when this drug is administered to patients with renal dysfunction.
DESCRIPTION Memantine is a non-competitive NMDA receptor antagonist approved for Alzheimer's disease but is also being studied in non-dementia psychiatric disorders . (GtoPdb)
PHARMACODYNAMICS **General effects**; ; This drug inhibits calcium influx into cells that is normally caused by chronic NMDA receptor activation by glutamate [A1640]. This leads to the improvement of Alzheimer's dementia symptoms, demonstrated by increased cognition and other beneficial central nervous system effects [A1640]. ; ; **Effects on neuroplasticity**; ; Like other NMDA receptor antagonists, memantine at high doses can reduce neuronal synaptic plasticity that is involved in learning and memory processes. At lower concentrations, which are normally used in the clinical setting, memantine can enhance neuronal synaptic plasticity in the brain, improve memory, and act as a neuroprotectant against the destruction of neurons caused by excitatory neurotransmitters [A1639]. ; ; **Effect on various receptors**; ; Memantine has demonstrated minimal activity for GABA, benzodiazepine, dopamine, adrenergic, histamine, and glycine receptors, as well as voltage-dependent Ca2+, Na+ or K+ channels. This drug has shown antagonist activity at the 5HT3 receptors. Laboratory studies suggest that memantine does not affect the reversible inhibition of the acetylcholinesterase normally caused by donepezil, galantamine, or tacrine [FDA label].
TOXICITY **LD50**; ; Oral LD50, mouse 437-498 mg/kg [F4375]; Oral LD50, rat 328-370 mg/kg [F4375]; ; **Carcinogenesis, Mutagenesis, Impairment of Fertility**; ; No evidence of carcinogenicity was seen in mouse and rat models administered memantine at doses equivalent to supratherapeutic human doses [FDA label]. Additionally, no genotoxic potential was noted when a battery of assays was performed. No effects on fertility or reproductive performance were noted in rats given to 18 mg/kg/day (equivalent to 9 times the maximum recommended human dose) orally from 14 days preceding mating through gestation and lactation in females, or for 60 preceding mating activity in males animals [FDA label].; ; **Use in pregnancy**; ; This drug is considered a pregnancy category B drug, meaning no sufficiently controlled and adequate studies of memantine in pregnant women have been performed. This drug should be taken during pregnancy only if the potential benefit justifies the possible fetal risk [FDA label]. ; ; **Use in nursing**; ; It is unknown whether memantine is excreted in human milk. Due to that fact that many drugs are found excreted in human milk, caution should be observed when this drug is taken by a nursing mother [FDA label].
DESCRIPTION Antagonist of NMDA glutamate receptors; stimulates dopamine release (LOPAC library)
DESCRIPTION NMDA antagonist; acts at ion channel site (Tocriscreen Total)
DESCRIPTION GABAA agonist (Tocris Bioactive Compound Library)
Cell lines
3
Organisms
2
Compound Sets
30
AdooQ Bioactive Compound Library
A11708
Cayman Chemical Bioactives
14184
25463
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL1699
CHEMBL807
ChEMBL Drugs
CHEMBL1699
CHEMBL807
CZ-OPENSCREEN Bioactive Library
DrugBank
DB01043
DrugBank Approved Drugs
DB01043
DrugCentral
1679
DrugCentral Approved Drugs
1679
DrugMAP
DMD9WSC
DrugMAP Approved Drugs
DMD9WSC
DrugMatrix
Enamine BioReference Compounds
Guide to Pharmacology
4253
Ki Database
Memantine
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL807
Mcule NIBR MoA Box Subset
MCULE-3726352671
NCATS Inxight Approved Drugs
W8O17SJF3T
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
memantine-hydrochloride-namenda
TargetMol Bioactive Compound Library
T1443
The Spectrum Collection
Tocris Bioactive Compound Library
0773
Tocriscreen Total
External IDs
64
Properties
(calculated by RDKit )
Molecular Weight
179.17
Hydrogen Bond Acceptors
1
Hydrogen Bond Donors
1
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
0
cLogP
2.69
TPSA
26.02
Fraction CSP3
1.0
Chiral centers
2.0
Largest ring
6.0
QED
0.61
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Selectivity
NMDA
Target
Autophagy
Cytochrome P450
iGluR
Glutamate [NMDA] receptor
AMPA
NMDA Receptor
Kainate receptor
CYP2B6
CYP2D6
NMDAR
Pathway
Metabolic Enzyme/Protease
Membrane Transporter/Ion Channel
Neuroscience
Metabolism
MOA
ionotropic glutamate receptor antagonist
Antagonist
NMDA Antagonists
Primary Target
NMDA Receptors
Member status
member
Source data