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
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
DescriptionSources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021169s031-021224s029-021615s022lbl.pdfCurator'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
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021169s031-021224s029-021615s022lbl.pdf
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.
CNS Activity
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12177686
Curator's Comment: # Janssen Pharmaceuticals, a division of Ortho-McNeil-Jannsen Pharmaceuticals
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL220 |
0.35 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | RAZADYNE Approved UseGalantamine hydrobromide is a cholinesterase inhibitor indicated for the treatment of mild to moderate dementia of the Alzheimer’s type. Launch Date9.833184E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
84.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16238894 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1050 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16238894 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8.53 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16238894 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
82% |
GALANTAMINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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%) Sources: Vomiting (21%) Diarrhea (16%) Anorexia (15%) Weight loss (8%) Dizziness (15%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical 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 | ||||
Page: 4, 20, (ClinPharm) 34, 38-39 |
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 2, 4, 19-20, (ClinPharm) 15, 38, 42-23, 45 |
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 |
||
Page: 2, 4, 19-20, (ClinPharm) 15, 38, 42-44 |
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
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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 |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1954303
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 | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
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
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
||
|
NDF-RT |
N0000175723
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
||
|
NDF-RT |
N0000000177
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
||
|
LIVERTOX |
NBK548544
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
||
|
WHO-ATC |
N06DA04
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
||
|
WHO-VATC |
QN06DA04
Created by
admin on Wed Jul 05 23:53:02 UTC 2023 , Edited by admin on Wed Jul 05 23:53:02 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
4637
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 | RxNorm | ||
|
0D3Q044KCA
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 | |||
|
DB00674
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 | |||
|
DTXSID2045606
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 | |||
|
100000084491
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 | |||
|
C65797
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 | |||
|
1392
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 | |||
|
0D3Q044KCA
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 | |||
|
1272
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 | |||
|
100058
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 | |||
|
M5640
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 | Merck Index | ||
|
6693
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 | |||
|
D005702
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 | |||
|
GALANTAMINE
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 | |||
|
MM-35
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 | |||
|
357-70-0
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 | |||
|
9651
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 | |||
|
7361
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 | |||
|
CHEMBL659
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 | |||
|
SUB07870MIG
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 | |||
|
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 |
ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
PRODRUG (METABOLITE ACTIVE)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)