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

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

[H][C@]12C[C@@H](O)C=C[C@]13CCN(C)CC4=CC=C(OC)C(O2)=C34

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

9.833184E11
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
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 90 years
Sex: M
Population Size: 1
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 1
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 90 years
Sex: M
Population Size: 1
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
n = 429
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: adult
Sex: unknown
Population Size: 429
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
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
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
Screening for acetylcholinesterase inhibitors from Amaryllidaceae using silica gel thin-layer chromatography in combination with bioactivity staining.
2001 Apr 27
Maintaining functional and behavioral abilities in Alzheimer disease.
2001 Aug
Medications for the treatment of Alzheimer's disease.
2001 Aug
Current status and new developments with galantamine in the treatment of Alzheimer's disease.
2001 Dec
Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's disease.
2001 Dec
Unsafe prescription medication switching recommendations.
2001 Dec
[Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors and gingko].
2001 Dec 13
Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic receptors: effects on the course of Alzheimer's disease.
2001 Feb 1
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
Galantamine (reminyl) for Alzheimer's disease.
2001 Jun 25
Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease.
2001 Mar 16
The pharmacological rationale for treating vascular dementia with galantamine (Reminyl).
2001 May
Meeting the challenges of vascular dementia. Introduction.
2001 May
Alzheimer's disease and related disorders.
2001 May
Galantamine: a new alzheimer drug with a past life.
2001 Nov
Galantamine hydrobromide.
2001 Nov 15
Galantamine: a randomized, double-blind, dose comparison in patients with Alzheimer's disease.
2001 Sep
Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy.
2002
Galantamine: a pharmacoeconomic review of its use in Alzheimer's disease.
2002
Economic analysis of galantamine, a cholinesterase inhibitor, in the treatment of patients with mild to moderate Alzheimer's disease in the Netherlands.
2002
Assessment of Health Economics in Alzheimer's Disease (AHEAD): treatment with galantamine in Sweden.
2002
Galantamine for Alzheimer's disease.
2002
A non-cholinergic, trophic action of acetylcholinesterase on hippocampal neurones in vitro: molecular mechanisms.
2002
Pharmacokinetics and safety of galantamine in subjects with hepatic impairment and healthy volunteers.
2002 Apr
Galantamine for vascular dementia: some answers, some questions.
2002 Apr 13
An efficient enantioselective synthesis of (-)-galanthamine.
2002 Aug 2
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
Switching cholinesterase inhibitors in patients with Alzheimer's disease.
2002 Jun
Pharmacologic treatments of dementia.
2002 May
The nicotinic allosteric potentiating ligand galantamine facilitates synaptic transmission in the mammalian central nervous system.
2002 May
[Latest therapies for treating dementia].
2002 May 15
Treatment options: the latest evidence with galantamine (Reminyl).
2002 Nov 15
Use of galantamine to treat vascular dementia.
2002 Nov 9
Acetylcholinesterase inhibitory activity of some Amaryllidaceae alkaloids and Narcissus extracts.
2002 Oct 11
A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat.
2002 Oct 25
Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer's disease with cerebrovascular disease after treatment with galantamine.
2002 Sep
Galantamine pharmacokinetics, safety, and tolerability profiles are similar in healthy Caucasian and Japanese subjects.
2002 Sep
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
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
NSC-100058
Code English
GALANTAMINE [VANDF]
Common Name English
GALANTAMINE [HSDB]
Common Name English
Classification Tree Code System Code
DSLD 4148 (Number of products:1)
Created by admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
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
Created by admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
PRIMARY