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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H21NO3
Molecular Weight 287.3535
Optical Activity ( - )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Galantamine

SMILES

COC1=CC=C2CN(C)CC[C@@]34C=C[C@H](O)C[C@@H]3OC1=C24

InChI

InChIKey=ASUTZQLVASHGKV-JDFRZJQESA-N
InChI=1S/C17H21NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,12,14,19H,7-10H2,1-2H3/t12-,14-,17-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68005702 | https://www.ncbi.nlm.nih.gov/pubmed/12177686

Galantamine (RAZADYNE®, galantamine hydrobromide) is a benzazepine derived from norbelladine. It is found in Galanthus and other Amaryllidaceae. It is a reversible, competitive acetylcholinesterase inhibitor that is used for the treatment of mild to moderate dementia of the Alzheimer’s type. Although the etiology of cognitive impairment in Alzheimer’s disease is not fully understood, it has been reported that acetylcholine-producing neurons degenerate in the brains of patients with Alzheimer’s disease. The degree of this cholinergic loss has been correlated with degree of cognitive impairment and density of amyloid plaques (a neuropathological hallmark of Alzheimer’s disease). While the precise mechanism of galantamine’s (RAZADYNE®, galantamine hydrobromide) action is unknown, it is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this mechanism is correct, galantamine’s (RAZADYNE®, galantamine hydrobromide) effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that galantamine (RAZADYNE®, galantamine hydrobromide) alters the course of the underlying dementing process.

Originator

Curator's Comment: # Janssen Pharmaceuticals, a division of Ortho-McNeil-Jannsen Pharmaceuticals

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.35 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
RAZADYNE

Approved Use

Galantamine hydrobromide is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type.

Launch Date

2001
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
84.3 ng/mL
24 mg single, oral
dose: 24 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GALANTAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1050 ng × h/mL
24 mg single, oral
dose: 24 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GALANTAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.53 h
24 mg single, oral
dose: 24 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
GALANTAMINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
82%
GALANTAMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
8 mg 2 times / day steady, oral
Dose: 8 mg, 2 times / day
Route: oral
Route: steady
Dose: 8 mg, 2 times / day
Sources:
unhealthy, 90 years
Health Status: unhealthy
Age Group: 90 years
Sex: M
Sources:
Disc. AE: Nightmares...
AEs leading to
discontinuation/dose reduction:
Nightmares (1 patient)
Sources:
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (42%)
Vomiting (21%)
Diarrhea (16%)
Anorexia (15%)
Weight loss (8%)
Dizziness (15%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nightmares 1 patient
Disc. AE
8 mg 2 times / day steady, oral
Dose: 8 mg, 2 times / day
Route: oral
Route: steady
Dose: 8 mg, 2 times / day
Sources:
unhealthy, 90 years
Health Status: unhealthy
Age Group: 90 years
Sex: M
Sources:
Anorexia 15%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dizziness 15%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Diarrhea 16%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Vomiting 21%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea 42%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Weight loss 8%
32 mg 1 times / day steady, oral
Highest studied dose
Dose: 32 mg, 1 times / day
Route: oral
Route: steady
Dose: 32 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [Activation 15.8489 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no
no
no
no
no (co-administration study)
Comment: Coadministration of Galantamine (multiple doses) had no effect on the pharmacokinetics of R-/S-Warfarin (CYP2C9 substrate)
Page: 4, 20, (ClinPharm) 34, 38-39
yes [IC50 0.6 uM]
no (co-administration study)
Comment: Coadministration of Galantamine (multiple doses) had no effect on the pharmacokinetics of Digoxin (P-gp substrate)
Page: 4, 20, (ClinPharm) 38, 40
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major [Km 187 uM]
yes (co-administration study)
Comment: Vmax = 5.2 nmol/mg protein/h (Pharmacogenetics, 9, 661 (1999)); Coadministration (multiple doses) of ketoconazole (strong CYP3A4 inhibitor, CYP2D6 inhibitor) and paroxetin (strong CYP2D6 inhibitor) increased Galantamine AUC by 30% and 40%.
Page: 2, 4, 19-20, (ClinPharm) 15, 38, 42-23, 45
major
yes (co-administration study)
Comment: Coadministration (multiple doses) of ketoconazole (strong CYP3A4 inhibitor, CYP2D6 inhibitor) increased Galantamine AUC by 30%. Coadministration of erythromycin (moderate CYP3A4 inhibitor) increased Galantamine AUC by only 10%.
Page: 2, 4, 19-20, (ClinPharm) 15, 38, 42-44
yes
Tox targets
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Accurate prediction of the bound conformation of galanthamine in the active site of Torpedo californica acetylcholinesterase using molecular docking.
2001
Pharmacokinetic rationale for switching from donepezil to galantamine.
2001
Therapeutic continuity in Alzheimer's disease: switching patients to galantamine. Panel discussion: recommendations for prescribers.
2001
Switching previous therapies for Alzheimer's disease to galantamine.
2001
Effects of washout and dose-escalation periods on the efficacy, safety, and tolerability of galantamine in patients previously treated with donepezil: ongoing clinical trials.
2001
Pharmacokinetic profiles of current therapies for Alzheimer's disease: implications for switching to galantamine.
2001
Therapeutic continuity in Alzheimer's disease: switching patients to galantamine. Introduction.
2001
Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.
2001 Apr
Maintaining functional and behavioral abilities in Alzheimer disease.
2001 Aug
Medications for the treatment of Alzheimer's disease.
2001 Aug
[Perspectives for drug treatment in Alzheimer's disease].
2001 Dec
Current status and new developments with galantamine in the treatment of Alzheimer's disease.
2001 Dec
[Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors and gingko].
2001 Dec 13
Galantamine introduced in Europe.
2001 Jan-Feb
Featured CME topic: dementia. Medication update.
2001 Jul
Use of cholinesterase inhibitors for treatment of Alzheimer disease.
2001 Jul
Use of biomimetic diversity-oriented synthesis to discover galanthamine-like molecules with biological properties beyond those of the natural product.
2001 Jul 11
Newest developments in dementia treatment and prevention.
2001 Jul-Aug
Galantamine (reminyl) for Alzheimer's disease.
2001 Jun 25
The pharmacological rationale for treating vascular dementia with galantamine (Reminyl).
2001 May
Meeting the challenges of vascular dementia. Introduction.
2001 May
[Anticholinesterase agents in Alzheimer's disease].
2001 Sep
Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence.
2001 Sep 1
Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy.
2002
Economic analysis of galantamine, a cholinesterase inhibitor, in the treatment of patients with mild to moderate Alzheimer's disease in the Netherlands.
2002
Galantamine for Alzheimer's disease.
2002
Cholinergic medication for neuroleptic-induced tardive dyskinesia.
2002
Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine.
2002
Unconventional ligands and modulators of nicotinic receptors.
2002 Dec
New drugs 2002, part 1.
2002 Jan
Pd asymmetric allylic alkylation (AAA). A powerful synthetic tool.
2002 Jan
A rapid TLC bioautographic method for the detection of acetylcholinesterase and butyrylcholinesterase inhibitors in plants.
2002 Jan-Feb
Medical treatment of Alzheimer's disease: past, present, and future.
2002 Jul
The efficacy of cholinesterase inhibitors in treating the behavioural symptoms of dementia.
2002 Jun
[Nicotinic Receptor, galantamine and Alzheimer disease].
2002 Jun 1-15
Pharmacologic treatments of dementia.
2002 May
[Treatment of Alzheimer's disease].
2002 Nov 1-15
The rationale behind cholinergic drug treatment for dementia related to cerebrovascular disease.
2002 Nov 15
Treatment options: the latest evidence with galantamine (Reminyl).
2002 Nov 15
Use of galantamine to treat vascular dementia.
2002 Nov 9
Use of galantamine to treat vascular dementia.
2002 Nov 9
Galantamine improved cognition and global functioning in vascular dementia or Alzheimer disease with cerebrovascular disease.
2002 Nov-Dec
Cognitive pharmacotherapy of Alzheimer's disease and other dementias.
2002 Oct
[Galantamine: a novel cholinergic agent for Alzheimer's disease].
2002 Oct
A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat.
2002 Oct 25
The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.
2002 Oct-Nov
Quaternary salts of E2020 analogues as acetylcholinesterase inhibitors for the reversal of neuromuscular block.
2002 Sep 16
Adjuvant galantamine administration improves negative symptoms in a patient with treatment-refractory schizophrenia.
2002 Sep-Oct
Clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for Alzheimer's disease. A systematic review.
2002 Summer
Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease.
2002 Summer
Patents

Sample Use Guides

The recommended starting dosage of RAZADYNE® tablets is 4 mg twice a day (8 mg/day). The dosage should be increased to the initial maintenance dosage of 8 mg twice a day (16 mg/day) after a minimum of 4 weeks. A further increase to 12 mg twice a day (24 mg/day) should be attempted after a minimum of 4 weeks at 8 mg twice a day (16 mg/day). Dosage increases should be based upon assessment of clinical benefit and tolerability of the previous dose.
Route of Administration: Oral
In Vitro Use Guide
Galanthamine was evaluated as inhibitor of human acetylcholinesterase activity from samples of postmortem human brain, fresh brain cortex biopsies and human erythrocytes. The respective galanthamine concentration exerting a half maximal effect (IC50) on acetylcholinesterase in postmortem human brain frontal cortex was 3.2 uM versus 2.8 uM in the hippocampus region. In addition, galanthamine was 10-fold less potent in inhibiting the enzyme activity from human brain that from human erythrocytes.
Name Type Language
Galantamine
HSDB   INN   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
NSC-100058
Preferred Name English
6H-BENZOFURO(3A,3,2-EF)(2)BENZAZEPIN-6-OL, 4A,5,9,10,11,12-HEXAHYDRO-3-METHOXY-11-METHYL-, (4AS,6R,8AS)
Common Name English
GALANTAMINE [USAN]
Common Name English
galantamine [INN]
Common Name English
(-)-GALANTHAMINE
Common Name English
Galantamine [WHO-DD]
Common Name English
(4aS,6R,8aS)-4a,5,9,10,11,12-Hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol
Common Name English
GALANTAMINE [MI]
Common Name English
GALANTHAMINE
Common Name English
(-)-GALANTAMINE
Common Name English
GALANTAMINE [VANDF]
Common Name English
GALANTAMINE [HSDB]
Common Name English
Classification Tree Code System Code
DSLD 4148 (Number of products:1)
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NCI_THESAURUS C47792
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NDF-RT N0000175723
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NDF-RT N0000000177
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LIVERTOX NBK548544
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WHO-ATC N06DA04
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WHO-VATC QN06DA04
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Code System Code Type Description
RXCUI
4637
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PRIMARY RxNorm
DAILYMED
0D3Q044KCA
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PRIMARY
DRUG BANK
DB00674
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PRIMARY
EPA CompTox
DTXSID2045606
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PRIMARY
SMS_ID
100000084491
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PRIMARY
NCI_THESAURUS
C65797
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PRIMARY
INN
1392
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PRIMARY
FDA UNII
0D3Q044KCA
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PRIMARY
DRUG CENTRAL
1272
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PRIMARY
NSC
100058
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PRIMARY
MERCK INDEX
m5640
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PRIMARY Merck Index
IUPHAR
6693
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PRIMARY
MESH
D005702
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PRIMARY
WIKIPEDIA
GALANTAMINE
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PRIMARY
USAN
MM-35
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PRIMARY
CAS
357-70-0
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PRIMARY
PUBCHEM
9651
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PRIMARY
HSDB
7361
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PRIMARY
ChEMBL
CHEMBL659
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PRIMARY
EVMPD
SUB07870MIG
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PRIMARY
CHEBI
42944
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PRIMARY