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

Molecular Formula C17H21NO3
Molecular Weight 287.3535
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Galantamine for Alzheimer's disease.
2001
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
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
Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.
2001
Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.
2001 Apr
FDA approves galantamine for Alzheimer's disease.
2001 Apr 15
Maintaining functional and behavioral abilities in Alzheimer disease.
2001 Aug
Maintaining cognitive function in Alzheimer disease: how effective are current treatments?
2001 Aug
Modulation of nicotinic receptor activity in the central nervous system: a novel approach to the treatment of Alzheimer disease.
2001 Aug
[Perspectives for drug treatment in Alzheimer's disease].
2001 Dec
Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's disease.
2001 Dec
Galantamine, a cholinesterase inhibitor that allosterically modulates nicotinic receptors: effects on the course of Alzheimer's disease.
2001 Feb 1
Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer's disease.
2001 Feb 1
Three-dimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: implications for the design of new anti-Alzheimer drugs.
2001 Feb 1
Galantamine introduced in Europe.
2001 Jan-Feb
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
APOE genotype: no influence on galantamine treatment efficacy nor on rate of decline in Alzheimer's disease.
2001 Mar-Apr
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
Effects of a flexible galantamine dose in Alzheimer's disease: a randomised, controlled trial.
2001 Nov
Galantamine hydrobromide.
2001 Nov 15
[Anticholinesterase agents in Alzheimer's disease].
2001 Sep
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
Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine.
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
Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.
2002 Apr 13
Unconventional ligands and modulators of nicotinic receptors.
2002 Dec
Medical treatment of Alzheimer's disease: past, present, and future.
2002 Jul
Galantamine for treatment-resistant schizophrenia.
2002 Jul
Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action.
2002 Jun
[Nicotinic Receptor, galantamine and Alzheimer disease].
2002 Jun 1-15
[Dementing disorders. What benefits do the new anti-dementia drugs have?].
2002 May 6
[Rivastigmine: a review of its clinical effectiveness].
2002 Nov 1-15
[Treatment of Alzheimer's disease].
2002 Nov 1-15
Use of galantamine to treat vascular dementia.
2002 Nov 9
Cognitive pharmacotherapy of Alzheimer's disease and other dementias.
2002 Oct
Acetylcholinesterase inhibitory activity of some Amaryllidaceae alkaloids and Narcissus extracts.
2002 Oct 11
The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.
2002 Oct-Nov
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
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
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.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:26:51 UTC 2023
Edited
by admin
on Fri Dec 15 16:26:51 UTC 2023
Record UNII
0D3Q044KCA
Record Status Validated (UNII)
Record Version
  • Download
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 Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
NCI_THESAURUS C47792
Created by admin on Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
NDF-RT N0000175723
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NDF-RT N0000000177
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LIVERTOX NBK548544
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WHO-ATC N06DA04
Created by admin on Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
WHO-VATC QN06DA04
Created by admin on Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
Code System Code Type Description
RXCUI
4637
Created by admin on Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
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
Created by admin on Fri Dec 15 16:26:51 UTC 2023 , Edited by admin on Fri Dec 15 16:26:51 UTC 2023
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
Related Record Type Details
TARGET -> INHIBITOR
IC50
OFF TARGET->NON-INHIBITOR
EXCRETED UNCHANGED
After i.v. or oral administration, about 20% of the dose was excreted as unchanged galantamine in the urine in 24 hours
AMOUNT EXCRETED
URINE
ENANTIOMER -> ENANTIOMER
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
BINDER->LIGAND
BINDING
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
O-demethylation, mediated by CYP2D6 was greater in extensive metabolizers of CYP2D6 than in poor metabolizers
MAJOR
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
PRODRUG -> METABOLITE ACTIVE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
PLASMA; URINE
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
PLASMA; URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
ORAL BIOAVAILABILITY PHARMACOKINETIC
Tmax PHARMACOKINETIC
blood to plasma ratio PHARMACOKINETIC