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
COC1=CC=C2CN(C)CC[C@@]34C=C[C@H](O)C[C@@H]3OC1=C24
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 Date2001 |
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 |
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 Health Status: unhealthy Age Group: adult Sex: unknown 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 |
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 Health Status: unhealthy Age Group: adult Sex: unknown 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 Health Status: unhealthy Age Group: adult Sex: unknown 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 Health Status: unhealthy Age Group: adult Sex: unknown 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 Health Status: unhealthy Age Group: adult Sex: unknown 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 Health Status: unhealthy Age Group: adult Sex: unknown 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 Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
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 |
---|---|---|
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 |
|
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 |
|
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 |
|
Muscarinic agonists and antagonists in the treatment of Alzheimer's disease. | 2001 Apr |
|
Maintaining functional and behavioral abilities in Alzheimer disease. | 2001 Aug |
|
Medications for the treatment of Alzheimer's disease. | 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 |
|
[Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors and gingko]. | 2001 Dec 13 |
|
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 |
|
Newest developments in dementia treatment and prevention. | 2001 Jul-Aug |
|
Galantamine (reminyl) for Alzheimer's disease. | 2001 Jun 25 |
|
The pharmacological rationale for treating vascular dementia with galantamine (Reminyl). | 2001 May |
|
Meeting the challenges of vascular dementia. Introduction. | 2001 May |
|
[Anticholinesterase agents in Alzheimer's disease]. | 2001 Sep |
|
Sleep and the cholinergic rapid eye movement sleep induction test in patients with primary alcohol dependence. | 2001 Sep 1 |
|
Nicotinic receptor modulation: advantages for successful Alzheimer's disease therapy. | 2002 |
|
Economic analysis of galantamine, a cholinesterase inhibitor, in the treatment of patients with mild to moderate Alzheimer's disease in the Netherlands. | 2002 |
|
Galantamine for Alzheimer's disease. | 2002 |
|
Cholinergic medication for neuroleptic-induced tardive dyskinesia. | 2002 |
|
Understanding and managing behavioural symptoms in Alzheimer's disease and related dementias: focus on rivastigmine. | 2002 |
|
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 |
|
A rapid TLC bioautographic method for the detection of acetylcholinesterase and butyrylcholinesterase inhibitors in plants. | 2002 Jan-Feb |
|
Medical treatment of Alzheimer's disease: past, present, and future. | 2002 Jul |
|
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 |
|
[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 |
|
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 |
|
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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N0000175723
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N0000000177
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NBK548544
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N06DA04
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QN06DA04
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C65797
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m5640
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D005702
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GALANTAMINE
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42944
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ACTIVE MOIETY
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