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Details

Stereochemistry ACHIRAL
Molecular Formula C13H14N2
Molecular Weight 198.2637
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TACRINE

SMILES

NC1=C2C=CC=CC2=NC3=C1CCCC3

InChI

InChIKey=YLJREFDVOIBQDA-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/cognex.html

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. 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. is used for the palliative treatment of mild to moderate dementia of the Alzheimer's type. Tacrine was marketed under the trade name Cognex. Because of its liver toxicity and attendant requirement for monitoring liver function, tacrine prescriptions dropped after other acetylcholinesterase inhibitors were introduced, and its use has been largely discontinued.

Originator

Curator's Comment: Originally developed by Warner-Lambert Co.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
500.0 nM [IC50]
23.0 nM [IC50]
0.46 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Cognex

Approved Use

Cognex® (tacrine hydrochloride capsules) is indicated for the treatment of mild to moderate dementia of the Alzheimer's type.

Launch Date

1993
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.8 ng/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TACRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
91.8 ng × h/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TACRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.8 h
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TACRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea (21 patient)
Vomiting (21 patient)
Anorexia (21 patient)
Dyspepsia (21 patient)
Diarrhea (21 patient)
Abdominal pain (21 patient)
Sources:
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Disc. AE: Transaminases increased, Atrial fibrillation...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (1 patient)
Atrial fibrillation (1 patient)
Dyspnea (1 patient)
Chest pain (1 patient)
Sources:
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Disc. AE: Transaminases increased, Nausea...
AEs leading to
discontinuation/dose reduction:
Transaminases increased (1 patient)
Nausea (1 patient)
Vomiting (1 patient)
Pallor (1 patient)
Vasodilatation (1 patient)
Sweating increased (1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Anorexia 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Diarrhea 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Dyspepsia 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Nausea 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Vomiting 21 patient
Disc. AE
160 mg 1 times / day multiple, oral
Highest studied dose
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy, 71.2 years (range: 52-88 years)
Health Status: unhealthy
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Sources:
Atrial fibrillation 1 patient
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Chest pain 1 patient
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Dyspnea 1 patient
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Transaminases increased 1 patient
Disc. AE
40 mg 1 times / day multiple, oral
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Nausea 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Pallor 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Sweating increased 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Transaminases increased 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Vasodilatation 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
Vomiting 1 patient
Disc. AE
80 mg 1 times / day multiple, oral
Recommended
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sources:
PubMed

PubMed

TitleDatePubMed
An appraisal of tacrine-extended suxamethonium.
1970 Feb
Ketamine-induced postanesthetic delirium attenuated by tetrahydroaminoacridine.
1974 Jul
Suxamethonium apnoea masked by tetrahydroaminacrine.
1978 Jul-Aug
Amino acridines action on Friend's retrovirus in relation to their molecular ionization.
1989
Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes.
1989 Nov 28
A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice.
1990 Nov
Synthesis and cholinergic properties of bis[[(dimethylamino)methyl]furanyl] analogues of ranitidine.
1992 Mar 20
Tacrine inhibits ventricular fibrillation induced by ischaemia and reperfusion and widens QT interval in rat.
1993 Mar
Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats.
1993 Nov 30
Severe parkinsonian symptom development on combination treatment with tacrine and haloperidol.
1995 Aug
Systemic administration of lithium chloride and tacrine but not kainic acid augments citrulline content of rat brain.
1995 Dec 27
Delirium caused by tacrine and ibuprofen interaction.
1996 Jun
Convulsive effects of tacrine.
1996 May 11
Adverse interaction of tacrine and haloperidol.
1996 Nov
Therapeutic approaches to age-associated neurocognitive disorders.
2001 Sep
Comparative effect of Prunus persica L. BATSCH-water extract and tacrine (9-amino-1,2,3,4-tetrahydroacridine hydrochloride) on concentration of extracellular acetylcholine in the rat hippocampus.
2003 Aug
Validation of the tremulous jaw movement model for assessment of the motor effects of typical and atypical antipychotics: effects of pimozide (Orap) in rats.
2005 Feb
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Evidence for the involvement of central serotonergic mechanisms in cholinergic tremor induced by tacrine in Balb/c mice.
2005 Sep 8
Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats.
2006
In vitro and in vivo characterization of F-97013-GD, a partial 5-HT1A agonist with antipsychotic- and antiparkinsonian-like properties.
2006 Jul
2006 Jun
Long-term tetrahydroaminoacridine treatment and quantitative EEG in Alzheimer's disease.
2007
WITHDRAWN: Tacrine for Alzheimer's disease.
2007 Jul 18
Allosteric modulation of muscarinic acetylcholine receptors.
2007 Sep
Effects of zonisamide on experimental tremors in rats.
2008
The investigation of structure-activity relationships of tacrine analogues: electronic-topological method.
2008 Aug 6
NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity.
2008 Dec 25
Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats.
2008 Jan
1-Phenyl-6,7,8,9-hexa-hydro-1H,5H-cyclo-hepta-[1',2':2,3]pyrido[6,5-c]pyrazol-4-amine: a new tacrine analogue.
2008 May 10
New performance of biosensor technology for Alzheimer's disease drugs: in vitro comparison of tacrine and 7-methoxytacrine.
2008 Oct
The 5-choice continuous performance test: evidence for a translational test of vigilance for mice.
2009
Cholinergic influence on memory stages: A study on scopolamine amnesic mice.
2009 Aug
Rapid determination of tacrine and other drug metabolites in microsomal incubate by newly developed targeting algorithm on UHPLC/TOFMS.
2009 Dec 15
Once-daily transdermal rivastigmine in the treatment of Alzheimer's disease.
2009 Feb 6
Identification of FDA-approved drugs and bioactives that protect hair cells in the zebrafish (Danio rerio) lateral line and mouse (Mus musculus) utricle.
2009 Jun
Coupling an HCN2-expressing cell to a myocyte creates a two-cell pacing unit.
2009 Nov 1
Contribution of the d-Serine-Dependent Pathway to the Cellular Mechanisms Underlying Cognitive Aging.
2010
Tacrine-NO donor and tacrine-ferulic acid hybrid molecules as new anti-Alzheimer agents: hepatotoxicity and influence on the cytochrome P450 system in comparison to tacrine.
2010
A second-generation device for automated training and quantitative behavior analyses of molecularly-tractable model organisms.
2010 Dec 17
Synthesis and AChE inhibitory activity of new chiral tetrahydroacridine analogues from terpenic cyclanones.
2010 Feb
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis.
2010 Jan 12
A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.
2010 Jan 18
Dual-acting drugs: an in vitro study of nonimidazole histamine H3 receptor antagonists combining anticholinesterase activity.
2010 Jul 5
Development of a highly sensitive cytotoxicity assay system for CYP3A4-mediated metabolic activation.
2011 Aug
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model.
2013 Dec
Inhibition of human carboxylesterases hCE1 and hiCE by cholinesterase inhibitors.
2013 Mar 25
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.
2014 Jan
N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice.
2015 Dec 5
Patents

Sample Use Guides

Oral Initially, 10 mg 4 times daily for at least 4 weeks. If well tolerated and increased serum ALT concentrations have not occurred, increase dosage to 20 mg 4 times daily; if tolerated, increase dosage in 40-mg daily increments (divided into 4 doses daily) at 4-week intervals up to a maximum of 160 mg daily (40 mg 4 times daily).
Route of Administration: Oral
Tacrine (0.01-10 uM) inhibited both human and rat HNMT activity in a concentration-dependent manner, but was less potent on both human embryonic kidney and recombinant human brain HNMT than on rat kidney HNMT (IC50 values were 0.46 and 0.70 uM vs. 0.29 uM, respectively).
Name Type Language
TACRINAL
Preferred Name English
TACRINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
Tacrine [WHO-DD]
Common Name English
TACRINE [VANDF]
Common Name English
tacrine [INN]
Common Name English
TACRINE [MI]
Common Name English
9-AMINO-1,2,3,4-TETRAHYDROACRIDINE
Systematic Name English
Classification Tree Code System Code
WHO-ATC N06DA01
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
NDF-RT N0000175723
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
WHO-VATC QN06DA01
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
NDF-RT N0000000177
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
NCI_THESAURUS C47792
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
LIVERTOX NBK547868
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
Code System Code Type Description
EPA CompTox
DTXSID1037272
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
CHEBI
45980
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
ChEMBL
CHEMBL95
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
PUBCHEM
1935
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
NCI_THESAURUS
C61961
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
MERCK INDEX
m10424
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY Merck Index
IUPHAR
6687
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
RXCUI
10318
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY RxNorm
SMS_ID
100000082994
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
ECHA (EC/EINECS)
206-291-2
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
EVMPD
SUB10796MIG
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
FDA UNII
4VX7YNB537
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
DRUG CENTRAL
2551
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
INN
800
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
CAS
321-64-2
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
MESH
D013619
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
WIKIPEDIA
TACRINE
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY
DRUG BANK
DB00382
Created by admin on Wed Apr 02 08:21:01 GMT 2025 , Edited by admin on Wed Apr 02 08:21:01 GMT 2025
PRIMARY