Identification

Name
Tacrine
Accession Number
DB00382  (APRD00690)
Type
Small Molecule
Groups
Investigational, Withdrawn
Description

A centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. Tacrine has been discontinued for the United States market.

Structure
Thumb
Synonyms
  • 1,2,3,4-tetrahydro-9-acridinamine
  • 1,2,3,4-tetrahydro-9-aminoacridine
  • 1,2,3,4-tetrahydroacridin-9-amine
  • 5-amino-6,7,8,9-tetrahydroacridine
  • 9-amino-1,2,3,4-tetrahydroacridine
  • Tacrin
  • Tacrine
  • Tacrinum
  • Tetrahydroaminacrine
  • Tetrahydroaminoacridine
  • THA
External IDs
CI 970
Product Ingredients
IngredientUNIICASInChI Key
Tacrine Hydrochloride4966RNG0BU1684-40-8ZUFVXZVXEJHHBN-UHFFFAOYSA-N
International/Other Brands
Cognex (Shionogi) / Talem (LKM)
Categories
UNII
4VX7YNB537
CAS number
321-64-2
Weight
Average: 198.2637
Monoisotopic: 198.115698458
Chemical Formula
C13H14N2
InChI Key
YLJREFDVOIBQDA-UHFFFAOYSA-N
InChI
InChI=1S/C13H14N2/c14-13-9-5-1-3-7-11(9)15-12-8-4-2-6-10(12)13/h1,3,5,7H,2,4,6,8H2,(H2,14,15)
IUPAC Name
1,2,3,4-tetrahydroacridin-9-amine
SMILES
NC1=C2CCCCC2=NC2=CC=CC=C12

Pharmacology

Indication

For the palliative treatment of mild to moderate dementia of the Alzheimer's type.

Structured Indications
Not Available
Pharmacodynamics

Tacrine is a parasympathomimetic- a reversible cholinesterase inhibitor that is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine at cholinergic synapses through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process.

Mechanism of action

The mechanism of tacrine is not fully known, but it is suggested that the drug is an anticholinesterase agent which reversibly binds with and inactivates cholinesterases. This inhibits the hydrolysis of acetylcholine released from functioning cholinergic neurons, thus leading to an accumulation of acetylcholine at cholinergic synapses. The result is a prolonged effect of acetylcholine.

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Human
ACholinesterase
inhibitor
Human
ULiver carboxylesterase 1Not AvailableHuman
Absorption

Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17%.

Volume of distribution
  • 349 ± 193 L
Protein binding

55%

Metabolism

Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity.

Route of elimination
Not Available
Half life

2 to 4 hours

Clearance
Not Available
Toxicity

Overdosage with cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. The estimated median lethal dose of tacrine following a single oral dose in rats is 40 mg/kg, or approximately 12 times the maximum recommended human dose of 160 mg/day.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when 16-Bromoepiandrosterone is combined with Tacrine.Investigational
19-norandrostenedioneThe risk or severity of adverse effects can be increased when 19-norandrostenedione is combined with Tacrine.Experimental, Illicit
5-androstenedioneThe risk or severity of adverse effects can be increased when 5-androstenedione is combined with Tacrine.Experimental, Illicit
AbirateroneThe serum concentration of Tacrine can be increased when it is combined with Abiraterone.Approved
AcebutololTacrine may increase the bradycardic activities of Acebutolol.Approved
AcetylcholineThe risk or severity of adverse effects can be increased when Tacrine is combined with Acetylcholine.Approved
AclidiniumThe therapeutic efficacy of Aclidinium can be decreased when used in combination with Tacrine.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Tacrine.Approved
AlclometasoneThe risk or severity of adverse effects can be increased when Alclometasone is combined with Tacrine.Approved
AlcuroniumThe therapeutic efficacy of Alcuronium can be decreased when used in combination with Tacrine.Experimental
AldosteroneThe risk or severity of adverse effects can be increased when Aldosterone is combined with Tacrine.Experimental, Investigational
AlprenololTacrine may increase the bradycardic activities of Alprenolol.Approved, Withdrawn
AmcinonideThe risk or severity of adverse effects can be increased when Amcinonide is combined with Tacrine.Approved
AndrostenedioneThe risk or severity of adverse effects can be increased when Androstenedione is combined with Tacrine.Experimental, Illicit
AnecortaveThe risk or severity of adverse effects can be increased when Anecortave is combined with Tacrine.Investigational
anecortave acetateThe risk or severity of adverse effects can be increased when anecortave acetate is combined with Tacrine.Investigational
Anisotropine MethylbromideThe therapeutic efficacy of Anisotropine Methylbromide can be decreased when used in combination with Tacrine.Approved
ArecolineThe risk or severity of adverse effects can be increased when Tacrine is combined with Arecoline.Experimental
ArotinololTacrine may increase the bradycardic activities of Arotinolol.Approved, Investigational
AtamestaneThe risk or severity of adverse effects can be increased when Atamestane is combined with Tacrine.Investigational
AtenololTacrine may increase the bradycardic activities of Atenolol.Approved
AtracuriumThe therapeutic efficacy of Atracurium can be decreased when used in combination with Tacrine.Experimental, Investigational
Atracurium besylateThe therapeutic efficacy of Atracurium besylate can be decreased when used in combination with Tacrine.Approved
AtropineThe therapeutic efficacy of Atropine can be decreased when used in combination with Tacrine.Approved, Vet Approved
AzithromycinThe metabolism of Tacrine can be decreased when combined with Azithromycin.Approved
Beclomethasone dipropionateThe risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Tacrine.Approved, Investigational
BefunololTacrine may increase the bradycardic activities of Befunolol.Experimental
BenactyzineThe therapeutic efficacy of Benactyzine can be decreased when used in combination with Tacrine.Withdrawn
BenzatropineThe therapeutic efficacy of Benzatropine can be decreased when used in combination with Tacrine.Approved
BetamethasoneThe risk or severity of adverse effects can be increased when Betamethasone is combined with Tacrine.Approved, Vet Approved
BetaxololTacrine may increase the bradycardic activities of Betaxolol.Approved
BethanecholThe risk or severity of adverse effects can be increased when Tacrine is combined with Bethanechol.Approved
BevantololTacrine may increase the bradycardic activities of Bevantolol.Approved
BiperidenThe therapeutic efficacy of Biperiden can be decreased when used in combination with Tacrine.Approved, Investigational
BisoprololTacrine may increase the bradycardic activities of Bisoprolol.Approved
BopindololTacrine may increase the bradycardic activities of Bopindolol.Approved
BornaprineThe therapeutic efficacy of Bornaprine can be decreased when used in combination with Tacrine.Experimental
BortezomibThe metabolism of Tacrine can be decreased when combined with Bortezomib.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Tacrine.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Tacrine.Approved
BucindololTacrine may increase the bradycardic activities of Bucindolol.Investigational
BudesonideThe risk or severity of adverse effects can be increased when Budesonide is combined with Tacrine.Approved
BufuralolTacrine may increase the bradycardic activities of Bufuralol.Experimental, Investigational
BupranololTacrine may increase the bradycardic activities of Bupranolol.Approved
CaffeineThe metabolism of Tacrine can be decreased when combined with Caffeine.Approved
CarbacholThe risk or severity of adverse effects can be increased when Tacrine is combined with Carbachol.Approved
CarteololTacrine may increase the bradycardic activities of Carteolol.Approved
CarvedilolTacrine may increase the bradycardic activities of Carvedilol.Approved, Investigational
CeliprololTacrine may increase the bradycardic activities of Celiprolol.Approved, Investigational
CevimelineThe risk or severity of adverse effects can be increased when Tacrine is combined with Cevimeline.Approved
ChlorphenoxamineThe therapeutic efficacy of Chlorphenoxamine can be decreased when used in combination with Tacrine.Withdrawn
CiclesonideThe risk or severity of adverse effects can be increased when Ciclesonide is combined with Tacrine.Approved, Investigational
CitalopramThe metabolism of Tacrine can be decreased when combined with Citalopram.Approved
ClobetasolThe risk or severity of adverse effects can be increased when Clobetasol is combined with Tacrine.Investigational
Clobetasol propionateThe risk or severity of adverse effects can be increased when Clobetasol propionate is combined with Tacrine.Approved
ClobetasoneThe risk or severity of adverse effects can be increased when Clobetasone is combined with Tacrine.Approved
ClocortoloneThe risk or severity of adverse effects can be increased when Clocortolone is combined with Tacrine.Approved
CloranololTacrine may increase the bradycardic activities of Cloranolol.Experimental
ClotrimazoleThe metabolism of Tacrine can be decreased when combined with Clotrimazole.Approved, Vet Approved
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Tacrine.Approved
Cortexolone 17α-propionateThe risk or severity of adverse effects can be increased when Cortexolone 17α-propionate is combined with Tacrine.Investigational
CorticosteroneThe risk or severity of adverse effects can be increased when Corticosterone is combined with Tacrine.Experimental
Cortisone acetateThe risk or severity of adverse effects can be increased when Cortisone acetate is combined with Tacrine.Approved
CyclopentolateThe therapeutic efficacy of Cyclopentolate can be decreased when used in combination with Tacrine.Approved
Cyproterone acetateThe serum concentration of Tacrine can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Tacrine.Approved
DarifenacinThe therapeutic efficacy of Darifenacin can be decreased when used in combination with Tacrine.Approved, Investigational
DeferasiroxThe serum concentration of Tacrine can be increased when it is combined with Deferasirox.Approved, Investigational
DeflazacortThe risk or severity of adverse effects can be increased when Deflazacort is combined with Tacrine.Approved
DesloratadineThe therapeutic efficacy of Desloratadine can be decreased when used in combination with Tacrine.Approved, Investigational
DesonideThe risk or severity of adverse effects can be increased when Desonide is combined with Tacrine.Approved, Investigational
DesoximetasoneThe risk or severity of adverse effects can be increased when Desoximetasone is combined with Tacrine.Approved
Desoxycorticosterone acetateThe risk or severity of adverse effects can be increased when Desoxycorticosterone acetate is combined with Tacrine.Approved
Desoxycorticosterone PivalateThe risk or severity of adverse effects can be increased when Desoxycorticosterone Pivalate is combined with Tacrine.Experimental, Vet Approved
DexamethasoneThe risk or severity of adverse effects can be increased when Dexamethasone is combined with Tacrine.Approved, Investigational, Vet Approved
Dexamethasone isonicotinateThe risk or severity of adverse effects can be increased when Dexamethasone isonicotinate is combined with Tacrine.Vet Approved
DexetimideThe therapeutic efficacy of Dexetimide can be decreased when used in combination with Tacrine.Withdrawn
DicyclomineThe therapeutic efficacy of Dicyclomine can be decreased when used in combination with Tacrine.Approved
DiflorasoneThe risk or severity of adverse effects can be increased when Diflorasone is combined with Tacrine.Approved
DifluocortoloneThe risk or severity of adverse effects can be increased when Difluocortolone is combined with Tacrine.Approved, Investigational
DifluprednateThe risk or severity of adverse effects can be increased when Difluprednate is combined with Tacrine.Approved
DipyridamoleThe therapeutic efficacy of Tacrine can be decreased when used in combination with Dipyridamole.Approved
DosulepinThe metabolism of Tacrine can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Tacrine.Approved, Investigational
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Tacrine.Approved
EmeproniumThe therapeutic efficacy of Emepronium can be decreased when used in combination with Tacrine.Experimental
EpanololTacrine may increase the bradycardic activities of Epanolol.Experimental
EpibatidineThe risk or severity of adverse effects can be increased when Tacrine is combined with Epibatidine.Experimental
EquileninThe risk or severity of adverse effects can be increased when Equilenin is combined with Tacrine.Experimental
EquilinThe risk or severity of adverse effects can be increased when Equilin is combined with Tacrine.Approved
EsmololTacrine may increase the bradycardic activities of Esmolol.Approved
EstroneThe risk or severity of adverse effects can be increased when Estrone is combined with Tacrine.Approved
Estrone sulfateThe risk or severity of adverse effects can be increased when Estrone sulfate is combined with Tacrine.Approved
EtanautineThe therapeutic efficacy of Etanautine can be decreased when used in combination with Tacrine.Experimental
EthopropazineThe therapeutic efficacy of Ethopropazine can be decreased when used in combination with Tacrine.Approved
EtybenzatropineThe therapeutic efficacy of Etybenzatropine can be decreased when used in combination with Tacrine.Experimental
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Tacrine.Approved
FesoterodineThe therapeutic efficacy of Fesoterodine can be decreased when used in combination with Tacrine.Approved
fluasteroneThe risk or severity of adverse effects can be increased when fluasterone is combined with Tacrine.Investigational
FludrocortisoneThe risk or severity of adverse effects can be increased when Fludrocortisone is combined with Tacrine.Approved
FlumethasoneThe risk or severity of adverse effects can be increased when Flumethasone is combined with Tacrine.Approved, Vet Approved
FlunisolideThe risk or severity of adverse effects can be increased when Flunisolide is combined with Tacrine.Approved, Investigational
Fluocinolone AcetonideThe risk or severity of adverse effects can be increased when Fluocinolone Acetonide is combined with Tacrine.Approved, Investigational, Vet Approved
FluocinonideThe risk or severity of adverse effects can be increased when Fluocinonide is combined with Tacrine.Approved, Investigational
FluocortoloneThe risk or severity of adverse effects can be increased when Fluocortolone is combined with Tacrine.Approved, Withdrawn
FluorometholoneThe risk or severity of adverse effects can be increased when Fluorometholone is combined with Tacrine.Approved
FluprednideneThe risk or severity of adverse effects can be increased when Fluprednidene is combined with Tacrine.Approved, Withdrawn
FluprednisoloneThe risk or severity of adverse effects can be increased when Fluprednisolone is combined with Tacrine.Approved
FlurandrenolideThe risk or severity of adverse effects can be increased when Flurandrenolide is combined with Tacrine.Approved
Fluticasone furoateThe risk or severity of adverse effects can be increased when Fluticasone furoate is combined with Tacrine.Approved
Fluticasone propionateThe risk or severity of adverse effects can be increased when Fluticasone propionate is combined with Tacrine.Approved
FluvoxamineThe metabolism of Tacrine can be decreased when combined with Fluvoxamine.Approved, Investigational
FormestaneThe risk or severity of adverse effects can be increased when Formestane is combined with Tacrine.Approved, Investigational, Withdrawn
GallamineThe therapeutic efficacy of Gallamine can be decreased when used in combination with Tacrine.Experimental
Gallamine TriethiodideThe therapeutic efficacy of Gallamine Triethiodide can be decreased when used in combination with Tacrine.Approved
GlycopyrroniumThe therapeutic efficacy of Glycopyrronium can be decreased when used in combination with Tacrine.Approved, Investigational, Vet Approved
GTS-21The risk or severity of adverse effects can be increased when Tacrine is combined with GTS-21.Investigational
HalcinonideThe risk or severity of adverse effects can be increased when Halcinonide is combined with Tacrine.Approved, Investigational, Withdrawn
HE3286The risk or severity of adverse effects can be increased when HE3286 is combined with Tacrine.Investigational
HexamethoniumThe therapeutic efficacy of Hexamethonium can be decreased when used in combination with Tacrine.Experimental
HomatropineThe therapeutic efficacy of Homatropine can be decreased when used in combination with Tacrine.Approved
HydrocortisoneThe risk or severity of adverse effects can be increased when Hydrocortisone is combined with Tacrine.Approved, Vet Approved
HyoscyamineThe therapeutic efficacy of Hyoscyamine can be decreased when used in combination with Tacrine.Approved
IndenololTacrine may increase the bradycardic activities of Indenolol.Withdrawn
Ipratropium bromideThe therapeutic efficacy of Ipratropium bromide can be decreased when used in combination with Tacrine.Approved
IstaroximeThe risk or severity of adverse effects can be increased when Istaroxime is combined with Tacrine.Investigational
LabetalolTacrine may increase the bradycardic activities of Labetalol.Approved
LandiololTacrine may increase the bradycardic activities of Landiolol.Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Tacrine.Approved
LevobunololTacrine may increase the bradycardic activities of Levobunolol.Approved
LidocaineThe metabolism of Tacrine can be decreased when combined with Lidocaine.Approved, Vet Approved
LobeglitazoneThe metabolism of Tacrine can be decreased when combined with Lobeglitazone.Approved, Investigational
LobelineThe risk or severity of adverse effects can be increased when Tacrine is combined with Lobeline.Investigational
LoteprednolThe risk or severity of adverse effects can be increased when Loteprednol is combined with Tacrine.Approved
MazaticolThe therapeutic efficacy of Mazaticol can be decreased when used in combination with Tacrine.Experimental
ME-609The risk or severity of adverse effects can be increased when ME-609 is combined with Tacrine.Investigational
MecamylamineThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with Tacrine.Approved
MedrysoneThe risk or severity of adverse effects can be increased when Medrysone is combined with Tacrine.Approved
MelengestrolThe risk or severity of adverse effects can be increased when Melengestrol is combined with Tacrine.Vet Approved
MepindololTacrine may increase the bradycardic activities of Mepindolol.Experimental
MethacholineThe risk or severity of adverse effects can be increased when Tacrine is combined with Methacholine.Approved
MethanthelineThe therapeutic efficacy of Methantheline can be decreased when used in combination with Tacrine.Approved, Investigational
MethylprednisoloneThe risk or severity of adverse effects can be increased when Methylprednisolone is combined with Tacrine.Approved, Vet Approved
Methylscopolamine bromideThe therapeutic efficacy of Methylscopolamine bromide can be decreased when used in combination with Tacrine.Approved
MetipranololTacrine may increase the bradycardic activities of Metipranolol.Approved
MetixeneThe therapeutic efficacy of Metixene can be decreased when used in combination with Tacrine.Approved
MetoprololTacrine may increase the bradycardic activities of Metoprolol.Approved, Investigational
MexiletineThe metabolism of Tacrine can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Tacrine can be decreased when combined with Midostaurin.Approved
MivacuriumTacrine may decrease the neuromuscular blocking activities of Mivacurium.Approved
MometasoneThe risk or severity of adverse effects can be increased when Mometasone is combined with Tacrine.Approved, Vet Approved
NadololTacrine may increase the bradycardic activities of Nadolol.Approved
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Tacrine.Approved
NCX 1022The risk or severity of adverse effects can be increased when NCX 1022 is combined with Tacrine.Investigational
NebivololTacrine may increase the bradycardic activities of Nebivolol.Approved, Investigational
NevirapineThe metabolism of Tacrine can be decreased when combined with Nevirapine.Approved
NicotineThe risk or severity of adverse effects can be increased when Tacrine is combined with Nicotine.Approved
Oleoyl-estroneThe risk or severity of adverse effects can be increased when Oleoyl-estrone is combined with Tacrine.Investigational
OrphenadrineThe therapeutic efficacy of Orphenadrine can be decreased when used in combination with Tacrine.Approved
OsimertinibThe serum concentration of Tacrine can be decreased when it is combined with Osimertinib.Approved
OtiloniumThe therapeutic efficacy of Otilonium can be decreased when used in combination with Tacrine.Experimental, Investigational
OxitropiumThe therapeutic efficacy of Oxitropium can be decreased when used in combination with Tacrine.Investigational
OxprenololTacrine may increase the bradycardic activities of Oxprenolol.Approved
OxybutyninThe therapeutic efficacy of Oxybutynin can be decreased when used in combination with Tacrine.Approved, Investigational
OxyphenoniumThe therapeutic efficacy of Oxyphenonium can be decreased when used in combination with Tacrine.Approved
PancuroniumThe therapeutic efficacy of Pancuronium can be decreased when used in combination with Tacrine.Approved
ParamethasoneThe risk or severity of adverse effects can be increased when Paramethasone is combined with Tacrine.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Tacrine.Approved
Peginterferon alfa-2bThe serum concentration of Tacrine can be increased when it is combined with Peginterferon alfa-2b.Approved
PenbutololTacrine may increase the bradycardic activities of Penbutolol.Approved, Investigational
PentoliniumThe therapeutic efficacy of Pentolinium can be decreased when used in combination with Tacrine.Approved
PhenglutarimideThe therapeutic efficacy of Phenglutarimide can be decreased when used in combination with Tacrine.Experimental
PilocarpineThe risk or severity of adverse effects can be increased when Tacrine is combined with Pilocarpine.Approved
PindololTacrine may increase the bradycardic activities of Pindolol.Approved
PipecuroniumThe therapeutic efficacy of Pipecuronium can be decreased when used in combination with Tacrine.Approved
PirenzepineThe therapeutic efficacy of Pirenzepine can be decreased when used in combination with Tacrine.Approved
Platelet Activating FactorTacrine may increase the bradycardic activities of Platelet Activating Factor.Experimental
PractololTacrine may increase the bradycardic activities of Practolol.Approved
PrasteroneThe risk or severity of adverse effects can be increased when Prasterone is combined with Tacrine.Approved, Nutraceutical
Prasterone sulfateThe risk or severity of adverse effects can be increased when Prasterone sulfate is combined with Tacrine.Investigational
PrednicarbateThe risk or severity of adverse effects can be increased when Prednicarbate is combined with Tacrine.Approved
PrednisoloneThe risk or severity of adverse effects can be increased when Prednisolone is combined with Tacrine.Approved, Vet Approved
PrednisoneThe risk or severity of adverse effects can be increased when Prednisone is combined with Tacrine.Approved, Vet Approved
PregnenoloneThe risk or severity of adverse effects can be increased when Pregnenolone is combined with Tacrine.Experimental, Investigational
ProcyclidineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with Tacrine.Approved
PropanthelineThe therapeutic efficacy of Propantheline can be decreased when used in combination with Tacrine.Approved
PropiverineThe therapeutic efficacy of Propiverine can be decreased when used in combination with Tacrine.Approved, Investigational
PropranololTacrine may increase the bradycardic activities of Propranolol.Approved, Investigational
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Tacrine.Approved
QuinidineThe therapeutic efficacy of Quinidine can be decreased when used in combination with Tacrine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Tacrine.Approved, Investigational
RapacuroniumTacrine may decrease the neuromuscular blocking activities of Rapacuronium.Withdrawn
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Tacrine.Approved, Investigational
RimexoloneThe risk or severity of adverse effects can be increased when Rimexolone is combined with Tacrine.Approved
RopiniroleThe metabolism of Tacrine can be decreased when combined with Ropinirole.Approved, Investigational
ScopolamineThe therapeutic efficacy of Scopolamine can be decreased when used in combination with Tacrine.Approved
Scopolamine butylbromideThe therapeutic efficacy of Scopolamine butylbromide can be decreased when used in combination with Tacrine.Approved, Vet Approved
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Tacrine.Approved
SimeprevirThe metabolism of Tacrine can be decreased when combined with Simeprevir.Approved
SolifenacinThe therapeutic efficacy of Solifenacin can be decreased when used in combination with Tacrine.Approved
SotalolTacrine may increase the bradycardic activities of Sotalol.Approved
SuccinylcholineThe serum concentration of Succinylcholine can be increased when it is combined with Tacrine.Approved
TalinololTacrine may increase the bradycardic activities of Talinolol.Investigational
Tenofovir disoproxilThe metabolism of Tacrine can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TeriflunomideThe serum concentration of Tacrine can be decreased when it is combined with Teriflunomide.Approved
TertatololTacrine may increase the bradycardic activities of Tertatolol.Experimental
TheophyllineThe metabolism of Tacrine can be decreased when combined with Theophylline.Approved
TiclopidineThe metabolism of Tacrine can be decreased when combined with Ticlopidine.Approved
TimololTacrine may increase the bradycardic activities of Timolol.Approved
TiotropiumThe therapeutic efficacy of Tiotropium can be decreased when used in combination with Tacrine.Approved
TixocortolThe risk or severity of adverse effects can be increased when Tixocortol is combined with Tacrine.Approved
TolterodineThe therapeutic efficacy of Tolterodine can be decreased when used in combination with Tacrine.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Tacrine.Approved, Investigational
TriamcinoloneThe risk or severity of adverse effects can be increased when Triamcinolone is combined with Tacrine.Approved, Vet Approved
TrihexyphenidylThe therapeutic efficacy of Trihexyphenidyl can be decreased when used in combination with Tacrine.Approved
TrimethaphanThe therapeutic efficacy of Trimethaphan can be decreased when used in combination with Tacrine.Approved, Investigational
TropatepineThe therapeutic efficacy of Tropatepine can be decreased when used in combination with Tacrine.Experimental
TropicamideThe therapeutic efficacy of Tropicamide can be decreased when used in combination with Tacrine.Approved
TrospiumThe therapeutic efficacy of Trospium can be decreased when used in combination with Tacrine.Approved
TubocurarineThe therapeutic efficacy of Tubocurarine can be decreased when used in combination with Tacrine.Approved
UlobetasolThe risk or severity of adverse effects can be increased when Ulobetasol is combined with Tacrine.Approved
UmeclidiniumThe therapeutic efficacy of Umeclidinium can be decreased when used in combination with Tacrine.Approved
VareniclineThe risk or severity of adverse effects can be increased when Tacrine is combined with Varenicline.Approved, Investigational
VecuroniumThe therapeutic efficacy of Vecuronium can be decreased when used in combination with Tacrine.Approved
VemurafenibThe serum concentration of Tacrine can be increased when it is combined with Vemurafenib.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Tacrine.Approved, Investigational
ZucapsaicinThe metabolism of Tacrine can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference

S. Shirley Yang, Wayne Boisvert, Nouman A. Muhammad, Jay Weiss, "Controlled release tacrine drug delivery systems and methods for preparing same." U.S. Patent US5576022, issued February, 1993.

US5576022
General References
  1. Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M: Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. [PubMed:9842955]
  2. Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: Drug Class Review: Alzheimer's Drugs: Final Report [Internet] . [PubMed:20480924]
External Links
Human Metabolome Database
HMDB14526
KEGG Drug
D08555
KEGG Compound
C01453
PubChem Compound
1935
PubChem Substance
46505487
ChemSpider
1859
BindingDB
8961
ChEBI
45980
ChEMBL
CHEMBL95
Therapeutic Targets Database
DAP000558
PharmGKB
PA451576
HET
THA
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tacrine
ATC Codes
N06DA01 — Tacrine
PDB Entries
1acj / 1mx1 / 2aow / 2aox / 4bds
MSDS
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Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2WithdrawnTreatmentDependence, Cocaine1

Pharmacoeconomics

Manufacturers
  • Shionogi pharma inc
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Cognex 10 mg capsule3.03USD capsule
Cognex 20 mg capsule3.03USD capsule
Cognex 40 mg capsule3.03USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)183.5 °CPhysProp
water solubility217 mg/LNot Available
logP2.71HANSCH,C ET AL. (1995)
pKa9.95 (at 20 °C)PERRIN,DD (1972)
Predicted Properties
PropertyValueSource
Water Solubility0.136 mg/mLALOGPS
logP3.13ALOGPS
logP2.63ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)8.95ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.91 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity61.74 m3·mol-1ChemAxon
Polarizability22.79 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9783
Blood Brain Barrier+0.978
Caco-2 permeable-0.5267
P-glycoprotein substrateNon-substrate0.6195
P-glycoprotein inhibitor INon-inhibitor0.9247
P-glycoprotein inhibitor IINon-inhibitor0.9103
Renal organic cation transporterNon-inhibitor0.5073
CYP450 2C9 substrateNon-substrate0.8532
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7248
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5541
Ames testAMES toxic0.9107
CarcinogenicityNon-carcinogens0.9404
BiodegradationNot ready biodegradable0.9773
Rat acute toxicity3.4207 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9351
hERG inhibition (predictor II)Non-inhibitor0.6164
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
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Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-453e4e963f034e9de4cf
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-256a5702a96325bc74f2
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0002-0900000000-af483bfb98e7e2b87b39
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-006t-0900000000-3c9902ca237f9c26a2fb
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-006x-0900000000-dec59115a19fdec78a9f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0900000000-c04cbf634e493a774cd5

Taxonomy

Description
This compound belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridines
Alternative Parents
4-aminoquinolines / Aminopyridines and derivatives / Benzenoids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Acridine / 4-aminoquinoline / Aminoquinoline / Aminopyridine / Benzenoid / Pyridine / Heteroaromatic compound / Azacycle / Organic nitrogen compound / Organopnictogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic amine, acridines (CHEBI:45980) / a small molecule (CPD-10887)

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Human
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. Davis KL: Alzheimer's disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington. Geriatrics. 1999 Feb;54(2):42-7; quiz 48. [PubMed:10024872]
  2. Wang H, Carlier PR, Ho WL, Wu DC, Lee NT, Li CP, Pang YP, Han YF: Effects of bis(7)-tacrine, a novel anti-Alzheimer's agent, on rat brain AChE. Neuroreport. 1999 Mar 17;10(4):789-93. [PubMed:10208549]
  3. Traykov L, Tavitian B, Jobert A, Boller F, Forette F, Crouzel C, Di Giamberardino L, Pappata S: In vivo PET study of cerebral [11C] methyl- tetrahydroaminoacridine distribution and kinetics in healthy human subjects. Eur J Neurol. 1999 May;6(3):273-8. [PubMed:10210906]
  4. Wang H, Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):27-30. [PubMed:10375753]
  5. Kosasa T, Kuriya Y, Matsui K, Yamanishi Y: Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol. 1999 Sep 10;380(2-3):101-7. [PubMed:10513568]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Takatori Y: [Mechanisms of neuroprotective effects of therapeutic acetylcholinesterase inhibitors used in treatment of Alzheimer's disease]. Yakugaku Zasshi. 2006 Aug;126(8):607-16. [PubMed:16880719]
  8. Du DM, Carlier PR: Development of bivalent acetylcholinesterase inhibitors as potential therapeutic drugs for Alzheimer's disease. Curr Pharm Des. 2004;10(25):3141-56. [PubMed:15544504]
  9. Krustev AD, Argirova MD, Getova DP, Turiiski VI, Prissadova NA: Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles. Can J Physiol Pharmacol. 2006 Nov;84(11):1133-8. [PubMed:17218977]
  10. Villarroya M, Garcia AG, Marco JL: New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer's disease. Curr Pharm Des. 2004;10(25):3177-84. [PubMed:15544507]
  11. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [PubMed:12871155]
  12. Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morsch AL, Morsch VM, Schetinger MR: Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71. Epub 2006 Jun 17. [PubMed:16860785]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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. Wang H, Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):27-30. [PubMed:10375753]
  2. Krustev AD, Argirova MD, Getova DP, Turiiski VI, Prissadova NA: Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles. Can J Physiol Pharmacol. 2006 Nov;84(11):1133-8. [PubMed:17218977]
  3. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [PubMed:12871155]
  4. Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morsch AL, Morsch VM, Schetinger MR: Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71. Epub 2006 Jun 17. [PubMed:16860785]
Details
3. Liver carboxylesterase 1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [PubMed:12725862]

Enzymes

Details
1. Cytochrome P450 1A2
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. [PubMed:19754423]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. [PubMed:12065442]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. [PubMed:12438524]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:36