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Details

Stereochemistry ABSOLUTE
Molecular Formula C17H21NO3.ClH
Molecular Weight 323.814
Optical Activity ( - )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GALANTAMINE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=USUHXXKCHSBMOS-XPSHAMGMSA-N
InChI=1S/C17H21NO3.ClH/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;1H/t12-,14-,17-;/m0./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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

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
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
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
[Anticholinesterase agents in 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
Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors.
2002
[New theory! Galantamine and nicotinic-cholinergic transmission].
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
Cholinergic medication for neuroleptic-induced tardive dyskinesia.
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
Galantamine for vascular dementia: some answers, some questions.
2002 Apr 13
To what degree does cognitive impairment in Alzheimer's disease predict dependence of patients on caregivers?
2002 Aug 19
An efficient enantioselective synthesis of (-)-galanthamine.
2002 Aug 2
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
Medical treatment of Alzheimer's disease: past, present, and future.
2002 Jul
Switching cholinesterase inhibitors in patients with Alzheimer's disease.
2002 Jun
The tolerability and safety of cholinesterase inhibitors in the treatment of dementia.
2002 Jun
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
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
[Dementing disorders. What benefits do the new anti-dementia drugs have?].
2002 May 6
Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomized trial.
2002 Nov
[Rivastigmine: a review of its clinical effectiveness].
2002 Nov 1-15
[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
The impact of journal advertisements on prescribers of cholinesterase inhibitors.
2002 Oct
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
The cholinergic approach for the treatment of vascular dementia: evidence from pre-clinical and clinical studies.
2002 Oct-Nov
Galantamine provides broad benefits in patients with 'advanced moderate' Alzheimer's disease (MMSE < or = 12) for up to six months.
2002 Sep
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
Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomized trial.
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
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 12:05:46 GMT 2023
Edited
by admin
on Sat Dec 16 12:05:46 GMT 2023
Record UNII
HV8VV786RM
Record Status Validated (UNII)
Record Version
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Name Type Language
GALANTAMINE HYDROCHLORIDE
MI   WHO-DD  
Common Name English
(-)-GALANTHAMINE HYDROCHLORIDE
Common Name English
6H-BENZOFURO(3A,3,2-EF)(2)BENZAZEPIN-6-OL, 4A,5,9,10,11,12-HEXAHYDRO-3-METHOXY-11-METHYL-, HYDROCHLORIDE (1:1), (4AS,6R,8AS)-
Systematic Name English
Galantamine hydrochloride [WHO-DD]
Common Name English
6H-BENZOFURO(3A,3,2-EF)(2)BENZAZEPIN-6-OL, 4A,5,9,10,11,12-HEXAHYDRO-3-METHOXY-11-METHYL-, HYDROCHLORIDE, (4AS,6R,8AS)-
Systematic Name English
GALANTAMINE HYDROCHLORIDE [MI]
Common Name English
GALANTHAMINE, HYDROCHLORIDE
Common Name English
Code System Code Type Description
PUBCHEM
11702557
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
FDA UNII
HV8VV786RM
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
MERCK INDEX
m5640
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
SMS_ID
300000033357
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
CAS
5072-47-9
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
EPA CompTox
DTXSID70470872
Created by admin on Sat Dec 16 12:05:46 GMT 2023 , Edited by admin on Sat Dec 16 12:05:46 GMT 2023
PRIMARY
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