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
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
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 |
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 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 |
---|---|---|
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 |
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 08:23:01 GMT 2023
by
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on
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Record UNII |
5N4SA4KQX9
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Record Status |
Validated (UNII)
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Record Version |
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PARENT -> SALT/SOLVATE |
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