Identification

Name
Galantamine
Accession Number
DB00674  (APRD00206, EXPT01628)
Type
Small Molecule
Groups
Approved
Description

Galantamine is a tertiary alkaloid and reversible, competitive inhibitor of the acetylcholinesterase (AChE) enzyme, which is a common therapeutic target used in the treatment of Alzheimer's disease.1 First characterized in the early 1950s, galantamine is a tertiary alkaloid that was first extracted from the botanical sources, such as Galanthus nivalis.7 Galantamine was first studied in paralytic and neuropathic conditions as a reverser of neuromuscular blockade.9,7 Following the discovery of its AChE-inhibiting properties, the drug was widely investigated for the use in the treatment of other psychiatric conditions.7 Galantamine also acts as an allosteric modulator of the nicotinic receptor, giving its dual mechanism of action clinical significance.9

The drug was approved by the FDA in 2001 for the treatment of mild to moderate dementia of the Alzheimer's type. As Alzheimer's disease is a progressive neurodegenerative disorder, galantamine is not known to alter the course of the underlying dementing process. Galantamine works to block the enzyme responsible for the breakdown of acetylcholine in the synaptic cleft, thereby enhancing cholinergic neuron function and signalling. Under this hypothesized mechanism of action, the therapeutic effects of galantamine may decrease as the disease progression advances and fewer cholinergic neurons remain functionally intact.12 It is therefore not considered to be a disease-modifying drug.10 Galantamine is marketed under the brand name Razadyne, and is available as oral immediate- and extended-release tablets and solution.12

Structure
Thumb
Synonyms
  • (-)-Galanthamine
  • Galantamina
  • Galantamine
  • Galanthamine
External IDs
NSC-100058
Product Ingredients
IngredientUNIICASInChI Key
Galantamine hydrobromideMJ4PTD2VVW1953-04-4QORVDGQLPPAFRS-XPSHAMGMSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Galantamine ERCapsule, extended releaseOralSanis Health Inc2016-01-11Not applicableCanada
Galantamine ERCapsule, extended releaseOralSanis Health Inc2016-01-11Not applicableCanada
Galantamine ERCapsule, extended releaseOralSanis Health Inc2016-01-11Not applicableCanada
Galantamine ERCapsule, extended releaseOralPro Doc Limitee2013-12-03Not applicableCanada
Galantamine ERCapsule, extended releaseOralPro Doc Limitee2013-12-03Not applicableCanada
Galantamine ERCapsule, extended releaseOralPro Doc Limitee2013-12-03Not applicableCanada
Galantamine HydrobromideCapsule, extended release16 mg/1OralPatriot Pharmaceuticals, LLC2004-12-22Not applicableUs
Galantamine HydrobromideCapsule, extended release8 mg/1OralPatriot Pharmaceuticals, LLC2004-12-22Not applicableUs
Galantamine HydrobromideTablet, film coated12 mg/1OralPatriot Pharmaceuticals, LLC2001-02-282020-09-30Us
Galantamine HydrobromideTablet, film coated8 mg/1OralPatriot Pharmaceuticals, LLC2001-02-282020-09-30Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-galantamineTabletOralApotex CorporationNot applicableNot applicableCanada
Apo-galantamineTabletOralApotex CorporationNot applicableNot applicableCanada
Apo-galantamineTabletOralApotex CorporationNot applicableNot applicableCanada
Auro-galantamine ERCapsule, extended releaseOralAuro Pharma Inc2014-06-12Not applicableCanada
Auro-galantamine ERCapsule, extended releaseOralAuro Pharma Inc2014-06-12Not applicableCanada
Auro-galantamine ERCapsule, extended releaseOralAuro Pharma Inc2014-06-12Not applicableCanada
GalantamineTablet, film coated12 mg/1OralTeva2008-08-282018-03-31Us00555 0140 09 nlmimage10 ee2b771b
GalantamineTablet, film coated4 mg/1OralRising Health, Llc2011-03-29Not applicableUs
GalantamineTablet, film coated8 mg/1OralApotex Corp.2012-11-052021-09-30Us
GalantamineTablet, film coated4 mg/1OralMylan Pharmaceuticals2010-02-192010-09-30Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Lycoremine / Nivalin / Reminyl
Categories
UNII
0D3Q044KCA
CAS number
357-70-0
Weight
Average: 287.3535
Monoisotopic: 287.152143543
Chemical Formula
C17H21NO3
InChI Key
ASUTZQLVASHGKV-JDFRZJQESA-N
InChI
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
IUPAC Name
(1S,12S,14R)-9-methoxy-4-methyl-11-oxa-4-azatetracyclo[8.6.1.0^{1,12}.0^{6,17}]heptadeca-6(17),7,9,15-tetraen-14-ol
SMILES
[H][C@]12C[C@@H](O)C=C[C@]11CCN(C)CC3=C1C(O2)=C(OC)C=C3

Pharmacology

Indication

Galantamine is indicated for the treatment of mild to moderate dementia of the Alzheimer’s type.12

Associated Conditions
Pharmacodynamics

Galantamine is a competitive and reversible inhibitor of acetylcholinesterase that works to increase acetylcholine levels.12 Galantamine is also an allosteric modulator of neuronal nicotinic acetylcholine receptors.7 As dementia is a progressive neurodegenerative disease, galatamine has a negligible effect in altering the course of the underlying process of dementia.12

Mechanism of action

Alzheimer’s disease is characterized by progressive, irreversible degeneration of acetylcholine-producing neurons, cognitive impairment, and the formation of amyloid plaques.9

10

Galantamine competitively and reversibly inhibits the anticholinesterase enzyme 12 by binding to the choline-binding site and acyl-binding pocket of the enzyme active site.2 Galantamine binds to the neuronal nicotinic acetylcholine receptors (nAChR) at a binding site that is different from acetylcholine binding site.11

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Humans
ANeuronal acetylcholine receptor subunit alpha-7
allosteric modulator
Humans
UMuscle nicotinic acetylcholine receptor
allosteric modulator
Humans
UCholinesterase
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Over a dose range of 8-32 mg/day, galantamine exhibits a dose-linear pharmacokinetic profile. The oral bioavailability of galantamine ranges from 90-100%. Following oral administration, the Tmax is about 1 hour.12 Following 10 hours of administration, the mean galantamine plasma concentrations were 82–97 µg/L for the 24 mg/day dose and 114–126 µg/L for the 32 mg/day dose.9

Volume of distribution

The mean volume of distribution is 175 L. About 52.7% of galantamine is distributed to blood cells, the blood to plasma concentration ratio of galantamine is 1.2.12

Protein binding

The plasma protein binding of galantamine is 18% at therapeutically relevant concentrations.12

Metabolism

In vitro study findings suggest that about 75% of the drug is metabolized by CYP2D6 and CYP3A4. CYP2D6 promotes O-demethylation of the drug to form O-desmethyl-galantamine and the CYP3A4-mediated pathway forms the galantamine-N-oxide.9 Other metabolites include norgalantamine, O-desmethyl-galantamine, O-desmethyl-norgalantamine, epigalantamine and galantaminone, which do not retain clinically significant pharmacology activities.5

Galantamine can also undergo glucuronidation: in one oral radiolabeled drug study in poor and extensive CYP2D6 metabolizers, about 14-24% of the total radioactivity was identified as galantamine glucuronide 8 hours post-dose. O-demethylation by CYP2D6 becomes prominent in patients with who are extensive metabolizers of CYP2D6, but unchanged galatamine (39-77%) and its glucuronide metabolite (14-24%) predominated in the plasma of both poor and extensive metabolizers of CYP2D6 in a radiolabelled drug study.12 The total plasma clearance, or nonrenal clearnace, accounts for 20–25% of drug elimination.9

Route of elimination

Following oral or intravenous administration, approximately 20% of the dose is excreted as unchanged in the urine within 24 h.9 In a radiolabelled drug study, about 95% and 5% of the total radioactivity was recovered in the urine and feces, respectively. Of the dose recovered in the urine, about 32% was in the unchanged parent compound, and 12% was in the glucuronide form.12

Half life

Galantamine has a terminal half-life of about 7 hours.12

Clearance

The renal clearance is 65 mL/min and the total plasma clearance is about 300 mL/min.9

Toxicity

The oral LD50 of the active ingredient, galantamine hydrobromide, in rats is 75 mg/kg.14 Symptoms of overdose are expected to be similar to those of cholinomimetics, which involve the central nervous system, the parasympathetic nervous system, and the neuromuscular junction. Effects of a cholinergic crisis include severe nausea, vomiting, gastrointestinal cramping, salivation, lacrimation, urination, defecation, sweating, bradycardia, hypotension, respiratory depression, collapse, and convulsions. Muscle weakness or fasciculations may also occur, with respiratory muscle weakness having the potential to bring fatal results. In one patient who consumed an oral daily dose of 32 mg developed bradycardia, QT prolongation, ventricular tachycardia and torsades de pointes accompanied by a brief loss of consciousness. In one patient with a history of hallucinations who consumed a daily dose of 24 mg galantamine, hallucinations requiring hospitalization occurred. A patient who ingested 160 mg of galantamine from an oral solution developed sweating, vomiting, bradycardia, and near-syncope one hour following consumption.12

As in any case of overdose, general supportive measures should be initiated. Tertiary anticholinergics such as intravenous atropine may be used to reverse the cholinergic effects of galantamine. The recommended initial dose of atropine intravenously administered for galantamine overdose ranges from 0.5 to 1.0 mg. It is not known whether galantamine can be removed by dialysis.12

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 3A4CYP3A4*20Not Available1461_1462insAEffect InferredPoor drug metabolizer.Details
Cytochrome P450 3A4CYP3A4*26Not Available802C>TEffect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Galantamine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Galantamine.
5-methoxy-N,N-dimethyltryptamineThe metabolism of 5-methoxy-N,N-dimethyltryptamine can be decreased when combined with Galantamine.
AbataceptThe metabolism of Galantamine can be increased when combined with Abatacept.
AbexinostatThe risk or severity of QTc prolongation can be increased when Galantamine is combined with Abexinostat.
AbirateroneThe metabolism of Galantamine can be decreased when combined with Abiraterone.
AcebutololThe risk or severity of QTc prolongation can be increased when Galantamine is combined with Acebutolol.
AceprometazineThe risk or severity of QTc prolongation can be increased when Galantamine is combined with Aceprometazine.
AcetaminophenThe metabolism of Galantamine can be decreased when combined with Acetaminophen.
AcetylcholineThe risk or severity of adverse effects can be increased when Galantamine is combined with Acetylcholine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

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  • Action
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Food Interactions
  • Take with food. Food delays the rate of absorption but not the extent.

References

Synthesis Reference

Vijaya Bolugoddu, Sanjay Shukla, Mukunda Jambula, Rajeshwar Sagyam, Ramchandra Pingili, Ananda Thirunavakarasu, "Preparation of (-)-galantamine hydrobromide." U.S. Patent US20060009640, issued January 12, 2006.

US20060009640
General References
  1. Scott LJ, Goa KL: Galantamine: a review of its use in Alzheimer's disease. Drugs. 2000 Nov;60(5):1095-122. [PubMed:11129124]
  2. Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEBS Lett. 1999 Dec 17;463(3):321-6. [PubMed:10606746]
  3. Woodruff-Pak DS, Vogel RW 3rd, Wenk GL: Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. Epub 2001 Feb 6. [PubMed:11172080]
  4. Birks J: Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. [PubMed:16437532]
  5. Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [PubMed:12177686]
  6. Olin J, Schneider L: Galantamine for Alzheimer's disease. Cochrane Database Syst Rev. 2002;(3):CD001747. [PubMed:12137632]
  7. Mucke HA: The case of galantamine: repurposing and late blooming of a cholinergic drug. Future Sci OA. 2015 Sep 3;1(4):FSO73. doi: 10.4155/fso.15.73. eCollection 2015 Nov. [PubMed:28031923]
  8. Mannens GS, Snel CA, Hendrickx J, Verhaeghe T, Le Jeune L, Bode W, van Beijsterveldt L, Lavrijsen K, Leempoels J, Van Osselaer N, Van Peer A, Meuldermans W: The metabolism and excretion of galantamine in rats, dogs, and humans. Drug Metab Dispos. 2002 May;30(5):553-63. doi: 10.1124/dmd.30.5.553. [PubMed:11950787]
  9. Farlow MR: Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92. doi: 10.2165/00003088-200342150-00005. [PubMed:14674789]
  10. Ferreira-Vieira TH, Guimaraes IM, Silva FR, Ribeiro FM: Alzheimer's disease: Targeting the Cholinergic System. Curr Neuropharmacol. 2016;14(1):101-15. doi: 10.2174/1570159x13666150716165726. [PubMed:26813123]
  11. Akk G, Steinbach JH: Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site. J Neurosci. 2005 Feb 23;25(8):1992-2001. doi: 10.1523/JNEUROSCI.4985-04.2005. [PubMed:15728839]
  12. FDA Approved Drug Products: RAZADYNE (galantamine hydrobromide), for oral use [Link]
  13. DailyMed Label: RAZADYNE - galantamine hydrobromide CAPSULE, EXTENDED RELEASE RAZADYNE - galantamine hydrobromide TABLET, FILM COATED [Link]
  14. Fisher Scientific: Galantamine hydrobromide MSDS [Link]
External Links
Human Metabolome Database
HMDB0014812
KEGG Drug
D04292
KEGG Compound
C08526
PubChem Compound
9651
PubChem Substance
46505659
ChemSpider
9272
BindingDB
10404
RxNav
4637
ChEBI
42944
ChEMBL
CHEMBL659
ZINC
ZINC000000491073
Therapeutic Targets Database
DAP000559
PharmGKB
PA449726
PDBe Ligand
GNT
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Galantamine
ATC Codes
N06DA04 — Galantamine
AHFS Codes
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
PDB Entries
1dx6 / 1qti / 1w6r / 1w76 / 2ph9 / 4ey6
FDA label
Download (278 KB)
MSDS
Download (28.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedTreatmentMethadone or Buprenorphine Detoxoxification1
1Active Not RecruitingBasic SciencePostural Tachycardia Syndrome1
1CompletedNot AvailableAlzheimer's Disease (AD)1
1CompletedNot AvailableHealthy Volunteers2
1CompletedScreeningMemory1
1CompletedTreatmentAlzheimer's Disease (AD)1
1CompletedTreatmentFasting1
1CompletedTreatmentFed1
1CompletedTreatmentPharmacokinetics1
1CompletedTreatmentSmoking / Tobacco Withdrawal1
1WithdrawnTreatmentInsulin Sensitivity / Oxidative Stress1
1, 2CompletedTreatmentBMI >30 kg/m21
1, 2CompletedTreatmentSubarachnoid Hemorrhage1
2Active Not RecruitingPreventionSchizophrenia1
2Active Not RecruitingTreatmentHIV Associated Cognitive Motor Complex1
2CompletedTreatmentDependence, Cocaine1
2CompletedTreatmentFrontotemporal Dementia / Pick Complex1
2CompletedTreatmentNicotine Addiction1
2CompletedTreatmentSchizophrenia2
2CompletedTreatmentTobacco Use Disorders1
2RecruitingDiagnosticPer Day for at Least the Past 6 Months / Treatment-seeking Smokers, Reporting Consumption of at Least 10 Cigarettes1
2RecruitingTreatmentCognitive Impairments / Stroke1
2TerminatedTreatmentPost Traumatic Stress Disorder (PTSD) / Traumatic Brain Injury (TBI)1
2TerminatedTreatmentSchizoaffective Disorders / Schizophrenia1
2, 3CompletedTreatmentSchizophrenia1
2, 3RecruitingNot AvailableDementia, Vascular / Mild Cognitive Disorder (Vascular) / Mild Cognitive Impairment (Vascular)1
3CompletedTreatmentAlzheimer's Disease (AD)7
3CompletedTreatmentAlzheimer's Disease (AD) / Brain Diseases / Dementias / Psychiatric Disorder NOS1
3CompletedTreatmentAlzheimer's Disease (AD) / Dementia, Vascular1
3CompletedTreatmentAlzheimer's Disease (AD) / Dementias9
3CompletedTreatmentAutism, Early Infantile1
3CompletedTreatmentBrain Diseases / Cognition Disorder / Nervous System Diseases / Psychiatric Disorder NOS1
3CompletedTreatmentDementia, Vascular1
3CompletedTreatmentDepression, Bipolar / Major Depressive Disorder (MDD) / Schizoaffective Disorders1
3CompletedTreatmentDiffuse Lewy Body Disease1
3CompletedTreatmentSchizophrenia1
3TerminatedTreatmentAlzheimer's Disease (AD)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenia1
4CompletedNot AvailableAlzheimer's Disease (AD)2
4CompletedNot AvailableAlzheimer's Disease (AD) / Dementia, Vascular / Dementias1
4CompletedNot AvailableAlzheimer's Disease (AD) / Dementias / Galantamine1
4CompletedTreatmentAbdominal Obesity Metabolic Syndrome1
4CompletedTreatmentAlzheimer's Disease (AD)5
4CompletedTreatmentAttention Deficit Disorder With Hyperactivity (ADHD)1
4CompletedTreatmentBipolar Disorder (BD)2
4CompletedTreatmentCerebrovascular Accident1
4CompletedTreatmentDementias1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenia2
4CompletedTreatmentTardive Dyskinesia (TD)1
4Not Yet RecruitingTreatmentAlzheimer's Disease (AD) / Cholinesterase Inhibitors1
4TerminatedBasic ScienceAlzheimer's Disease (AD)1
4TerminatedTreatmentAlzheimer's Disease (AD)1
4TerminatedTreatmentDepression1
4TerminatedTreatmentGilles de la Tourette's Syndrome / Motor Tic Disorder / Vocal Tic Disorder1
4TerminatedTreatmentPsychotic Disorder NOS / Schizophrenia1
4Unknown StatusNot AvailableAlzheimer's Disease (AD) / Dementias1
4Unknown StatusTreatmentAlzheimer's Disease (AD)1
4Unknown StatusTreatmentHead Trauma,Closed / Post-Traumatic Headaches / Retention Disorders, Cognitive1
Not AvailableCompletedNot AvailableBiomarkers, Pharmacological1
Not AvailableCompletedNot AvailableDiffuse Lewy Body Disease1
Not AvailableCompletedBasic ScienceBasic Science Study of the Mechanisms of Attentional Enhancement by Compounds Acting on the Nicotinic Receptor1
Not AvailableCompletedTreatmentAddictions1
Not AvailableCompletedTreatmentAphasia / Stroke1
Not AvailableCompletedTreatmentBipolar Disorder (BD)1
Not AvailableCompletedTreatmentChronic Schizophrenia1
Not AvailableCompletedTreatmentCocaine Abuse1
Not AvailableCompletedTreatmentDementias1
Not AvailableCompletedTreatmentNicotine Dependence1
Not AvailableTerminatedTreatmentAlzheimer's Disease (AD) / Dementias1
Not AvailableUnknown StatusDiagnosticAlzheimer's Disease (AD)1
Not AvailableUnknown StatusPreventionParkinson's Disease (PD)1

Pharmacoeconomics

Manufacturers
  • Barr laboratories inc
  • Impax laboratories inc
  • Watson laboratories inc
  • Ortho mcneil janssen pharmaceuticals inc
  • Roxane laboratories inc
  • Ortho mcneil janssen pharmaceutical inc
  • Actavis elizabeth llc
  • Beijing yabao biopharmaceutical co ltd
  • Dr reddys laboratories ltd
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa
Packagers
  • Alphapharm Party Ltd.
  • Barr Pharmaceuticals
  • Cardinal Health
  • DispenseXpress Inc.
  • Doctor Reddys Laboratories Ltd.
  • Global Pharmaceuticals
  • Heartland Repack Services LLC
  • Impax Laboratories Inc.
  • Janssen-Ortho Inc.
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Ortho Mcneil Janssen Pharmaceutical Inc.
  • Ortho-McNeil-Janssen Pharmaceuticals Inc.
  • Patriot Pharmaceuticals
  • Physician Partners Ltd.
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral12 mg/1
TabletOral4 mg/1
TabletOral8 mg/1
Tablet, film coatedOral12 mg/1
Tablet, film coatedOral4 mg/1
Tablet, film coatedOral8 mg/1
Capsule, extended releaseOral24 mg/1
Capsule, extended releaseOral8 mg/1
Capsule, extended releaseOral
Capsule, extended releaseOral16 mg/1
SolutionOral4 mg/1mL
TabletOral
Prices
Unit descriptionCostUnit
Galantamine Hydrobromide 30 16 mg 24 Hour Capsule Bottle198.58USD bottle
Galantamine Hydrobromide 30 8 mg 24 Hour Capsule Bottle198.58USD bottle
Razadyne 12 mg tablet8.3USD tablet
Razadyne 4 mg tablet5.36USD tablet
Razadyne 8 mg tablet3.66USD tablet
Galantamine hbr 12 mg tablet3.18USD tablet
Galantamine hbr 4 mg tablet3.18USD tablet
Galantamine hbr 8 mg tablet3.18USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2358062No2006-12-192019-12-20Canada
CA2310926No2001-11-202017-06-06Canada
US6358527No2002-03-192017-06-06Us
US6099863No2000-08-082017-06-06Us
US7160559No2007-01-092019-12-20Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
logP1.16ChemAxon
pKa (Strongest Acidic)14.81ChemAxon
pKa (Strongest Basic)8.58ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area41.93 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity82.3 m3·mol-1ChemAxon
Polarizability31.5 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9959
Caco-2 permeable+0.8259
P-glycoprotein substrateSubstrate0.8976
P-glycoprotein inhibitor IInhibitor0.6069
P-glycoprotein inhibitor IINon-inhibitor0.9443
Renal organic cation transporterInhibitor0.5728
CYP450 2C9 substrateNon-substrate0.8072
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.5414
CYP450 2C19 inhibitorNon-inhibitor0.8301
CYP450 3A4 inhibitorNon-inhibitor0.8832
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9439
Ames testNon AMES toxic0.7995
CarcinogenicityNon-carcinogens0.9055
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7790 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8023
hERG inhibition (predictor II)Non-inhibitor0.7424
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-000l-5980000000-928ad889466b6a2b3827
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0390000000-f4f443a7f842d92dec39

Taxonomy

Description
This compound belongs to the class of organic compounds known as galanthamine-type amaryllidaceae alkaloids. These are amaryllidaceae alkaloids with a structure characterized a tetracyclic skeleton with two ortho aromatic protons in ring A.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Amaryllidaceae alkaloids
Sub Class
Galanthamine-type amaryllidaceae alkaloids
Direct Parent
Galanthamine-type amaryllidaceae alkaloids
Alternative Parents
Benzazepines / Coumarans / Anisoles / Azepines / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Secondary alcohols / Oxacyclic compounds / Azacyclic compounds
show 2 more
Substituents
Galanthamine-type amaryllidaceae alkaloid / Benzazepine / Coumaran / Anisole / Alkyl aryl ether / Azepine / Aralkylamine / Benzenoid / Secondary alcohol / Tertiary amine
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound, organic heterotetracyclic compound, benzazepine alkaloid, benzazepine alkaloid fundamental parent (CHEBI:42944) / Isoquinoline alkaloids (C08526)

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Tonkopii VD, Prozorovskii VB, Suslova IM: [Interaction of reversible inhibitors with the catalytic centers and allosteric sites of cholinesterases]. Biull Eksp Biol Med. 1976 Aug;82(8):947-50. [PubMed:1026294]
  2. Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEBS Lett. 1999 Dec 17;463(3):321-6. [PubMed:10606746]
  3. Guillou C, Mary A, Renko DZ, Gras E, Thal C: Potent acetylcholinesterase inhibitors: design, synthesis and structure-activity relationships of alkylene linked bis-galanthamine and galanthamine-galanthaminium salts. Bioorg Med Chem Lett. 2000 Apr 3;10(7):637-9. [PubMed:10762042]
  4. Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [PubMed:12177686]
  5. Lilienfeld S, Parys W: Galantamine: additional benefits to patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2000 Sep;11 Suppl 1:19-27. [PubMed:10971048]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Allosteric modulator
Curator comments
Galantamine binding site is different from the ACh binding site.
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Lilienfeld S, Parys W: Galantamine: additional benefits to patients with Alzheimer's disease. Dement Geriatr Cogn Disord. 2000 Sep;11 Suppl 1:19-27. [PubMed:10971048]
  2. Woodruff-Pak DS, Lander C, Geerts H: Nicotinic cholinergic modulation: galantamine as a prototype. CNS Drug Rev. 2002 Winter;8(4):405-26. [PubMed:12481195]
  3. Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [PubMed:12177686]
  4. Ludwig J, Hoffle-Maas A, Samochocki M, Luttmann E, Albuquerque EX, Fels G, Maelicke A: Localization by site-directed mutagenesis of a galantamine binding site on alpha7 nicotinic acetylcholine receptor extracellular domain. J Recept Signal Transduct Res. 2010 Dec;30(6):469-83. doi: 10.3109/10799893.2010.505239. Epub 2010 Nov 9. [PubMed:21062106]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Allosteric modulator
General Function
Not Available
Specific Function
Extracellular ligand-gated ion channel activity
Gene Name
Not Available
Uniprot ID
A9X444
Uniprot Name
Muscle nicotinic acetylcholine receptor
Molecular Weight
10252.8 Da
References
  1. Akk G, Steinbach JH: Galantamine activates muscle-type nicotinic acetylcholine receptors without binding to the acetylcholine-binding site. J Neurosci. 2005 Feb 23;25(8):1992-2001. doi: 10.1523/JNEUROSCI.4985-04.2005. [PubMed:15728839]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Svoboda Z, Kvetina J, Kunesova G, Herink J, Bajgar J, Bartosova L, Zivny P, Palicka V: Effect of galantamine on acetylcholinesterase and butyrylcholinesterase activities in the presence of L-carnitine in rat selected brain and peripheral tissues. Neuro Endocrinol Lett. 2006 Dec;27 Suppl 2:183-6. [PubMed:17159811]
  2. Giacobini E: Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer's disease? Drugs Aging. 2001;18(12):891-8. [PubMed:11888344]
  3. Wilkinson DG: Galantamine: a new treatment for Alzheimer's disease. Expert Rev Neurother. 2001 Nov;1(2):153-9. doi: 10.1586/14737175.1.2.153. [PubMed:19811027]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jann MW, Shirley KL, Small GW: Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin Pharmacokinet. 2002;41(10):719-39. doi: 10.2165/00003088-200241100-00003. [PubMed:12162759]
  2. Farlow MR: Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92. doi: 10.2165/00003088-200342150-00005. [PubMed:14674789]
  3. Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [PubMed:12177686]
  4. Piotrovsky V, Van Peer A, Van Osselaer N, Armstrong M, Aerssens J: Galantamine population pharmacokinetics in patients with Alzheimer's disease: modeling and simulations. J Clin Pharmacol. 2003 May;43(5):514-23. [PubMed:12751272]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Jann MW, Shirley KL, Small GW: Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin Pharmacokinet. 2002;41(10):719-39. doi: 10.2165/00003088-200241100-00003. [PubMed:12162759]
  2. Farlow MR: Clinical pharmacokinetics of galantamine. Clin Pharmacokinet. 2003;42(15):1383-92. doi: 10.2165/00003088-200342150-00005. [PubMed:14674789]
  3. Lilienfeld S: Galantamine--a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer's disease. CNS Drug Rev. 2002 Summer;8(2):159-76. [PubMed:12177686]
  4. Piotrovsky V, Van Peer A, Van Osselaer N, Armstrong M, Aerssens J: Galantamine population pharmacokinetics in patients with Alzheimer's disease: modeling and simulations. J Clin Pharmacol. 2003 May;43(5):514-23. [PubMed:12751272]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Namanja HA, Emmert D, Pires MM, Hrycyna CA, Chmielewski J: Inhibition of human P-glycoprotein transport and substrate binding using a galantamine dimer. Biochem Biophys Res Commun. 2009 Oct 30;388(4):672-6. doi: 10.1016/j.bbrc.2009.08.056. Epub 2009 Aug 14. [PubMed:19683513]

Drug created on June 13, 2005 07:24 / Updated on May 26, 2020 16:49

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