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Details

Stereochemistry RACEMIC
Molecular Formula C17H21NO3.BrH
Molecular Weight 368.265
Optical Activity ( + / - )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GALANTAMINE HYDROBROMIDE, (±)-

SMILES

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

InChI

InChIKey=QORVDGQLPPAFRS-XPSHAMGMSA-N
InChI=1S/C17H21NO3.BrH/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 BrH
Molecular Weight 80.912
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 RACEMIC
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
Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution.
1999 Dec 17
Switching previous therapies for Alzheimer's disease 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
Maintaining cognitive function in Alzheimer disease: how effective are current treatments?
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
Allosteric sensitization of nicotinic receptors by galantamine, a new treatment strategy for Alzheimer's disease.
2001 Feb 1
Galantamine introduced in Europe.
2001 Jan-Feb
Use of cholinesterase inhibitors for treatment of Alzheimer disease.
2001 Jul
Newest developments in dementia treatment and prevention.
2001 Jul-Aug
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
Effects of a flexible galantamine dose in Alzheimer's disease: a randomised, controlled trial.
2001 Nov
[Anticholinesterase agents in Alzheimer's disease].
2001 Sep
Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy.
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
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
An efficient enantioselective synthesis of (-)-galanthamine.
2002 Aug 2
Pd asymmetric allylic alkylation (AAA). A powerful synthetic tool.
2002 Jan
Galanthamine as bis-functional ligand for the acetylcholinesterase.
2002 Jun
Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action.
2002 Jun
Pharmacologic treatments of dementia.
2002 May
[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
Cognitive pharmacotherapy of Alzheimer's disease and other dementias.
2002 Oct
[Galantamine: a novel cholinergic agent for Alzheimer's disease].
2002 Oct
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
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
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 08:23:01 GMT 2023
Edited
by admin
on Sat Dec 16 08:23:01 GMT 2023
Record UNII
5N4SA4KQX9
Record Status Validated (UNII)
Record Version
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Name Type Language
GALANTAMINE HYDROBROMIDE, (±)-
Common Name English
(±)-GALANTHAMINE HYDROBROMIDE
Common Name English
6H-BENZOFURO(3A,3,2-EF)(2)BENZAZEPIN-6-OL, 4A,5,9,10,11,12-HEXAHYDRO-3-METHOXY-11-METHYL-, HYDROBROMIDE (1:1), (4AR,6S,8AR)-REL-
Systematic Name English
GALANTAMINE HYDROBROMIDE (RACEMIC)
Common Name English
(±)-GALANTAMINE HYDROBROMIDE
Common Name English
6H-BENZOFURO(3A,3,2-EF)(2)BENZAZEPIN-6-OL, 4A,5,9,10,11,12-HEXAHYDRO-3-METHOXY-11-METHYL-, HYDROBROMIDE, (4A.ALPHA.,6.BETA.,8AR*)-
Systematic Name English
GALANTAMINE HYDROBROMIDE RACEMIC [USP-RS]
Common Name English
Code System Code Type Description
CAS
193146-85-9
Created by admin on Sat Dec 16 08:23:01 GMT 2023 , Edited by admin on Sat Dec 16 08:23:01 GMT 2023
PRIMARY
FDA UNII
5N4SA4KQX9
Created by admin on Sat Dec 16 08:23:01 GMT 2023 , Edited by admin on Sat Dec 16 08:23:01 GMT 2023
PRIMARY
PUBCHEM
121587
Created by admin on Sat Dec 16 08:23:01 GMT 2023 , Edited by admin on Sat Dec 16 08:23:01 GMT 2023
PRIMARY
RS_ITEM_NUM
1287766
Created by admin on Sat Dec 16 08:23:01 GMT 2023 , Edited by admin on Sat Dec 16 08:23:01 GMT 2023
PRIMARY
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