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 |
---|---|---|
[Perspectives for drug treatment in Alzheimer's disease]. | 2001 Dec |
|
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 |
|
Galantamine for Alzheimer's disease. | 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 |
|
Medical treatment of Alzheimer's disease: past, present, and future. | 2002 Jul |
|
Galanthamine as bis-functional ligand for the acetylcholinesterase. | 2002 Jun |
|
Switching cholinesterase inhibitors in patients with Alzheimer's disease. | 2002 Jun |
|
Evidence that the clinical effects of cholinesterase inhibitors are related to potency and targeting of action. | 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 |
|
The metabolism and excretion of galantamine in rats, dogs, and humans. | 2002 May |
|
[Latest therapies for treating dementia]. | 2002 May 15 |
|
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 |
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.
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Classification Tree | Code System | Code | ||
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DSLD |
4148 (Number of products:1)
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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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4637
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0D3Q044KCA
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DB00674
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DTXSID2045606
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C65797
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1392
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0D3Q044KCA
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1272
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100058
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M5640
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6693
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D005702
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GALANTAMINE
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MM-35
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357-70-0
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9651
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7361
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CHEMBL659
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SUB07870MIG
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42944
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