U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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

7.474464E11
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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: Page: p. 5
unhealthy, adult
n = 146
Health Status: unhealthy
Age Group: adult
Population Size: 146
Sources: Page: p. 5
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: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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)
n = 64
Health Status: unhealthy
Condition: Alzheimer's disease
Age Group: 71.2 years (range: 52-88 years)
Sex: M+F
Population Size: 64
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: Page: p. 5
unhealthy, adult
n = 146
Health Status: unhealthy
Age Group: adult
Population Size: 146
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 146
Health Status: unhealthy
Age Group: adult
Population Size: 146
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 146
Health Status: unhealthy
Age Group: adult
Population Size: 146
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 146
Health Status: unhealthy
Age Group: adult
Population Size: 146
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
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: Page: p. 5
unhealthy, adult
n = 150
Health Status: unhealthy
Age Group: adult
Population Size: 150
Sources: Page: p. 5
PubMed

PubMed

TitleDatePubMed
Suxamethonium apnoea masked by tetrahydroaminacrine.
1978 Jul-Aug
Amino acridines action on Friend's retrovirus in relation to their molecular ionization.
1989
Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats.
1992
Synthesis and cholinergic properties of bis[[(dimethylamino)methyl]furanyl] analogues of ranitidine.
1992 Mar 20
Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats.
1993 Nov 30
Systemic administration of lithium chloride and tacrine but not kainic acid augments citrulline content of rat brain.
1995 Dec 27
Adverse interaction of tacrine and haloperidol.
1996 Nov
Nicotine and sensory memory in Alzheimer's disease: an event-related potential study.
2002 Jul
Tacrine attenuates hydrogen peroxide-induced apoptosis by regulating expression of apoptosis-related genes in rat PC12 cells.
2002 Oct 30
Inhibition of human cholinesterases by drugs used to treat Alzheimer disease.
2003 Apr-Jun
Reduction in distractibility with AF102B and THA in the macaque.
2003 Sep
Cholinesterase inhibitors modify the activity of intrinsic cardiac neurons.
2004 Aug
Choline pivaloyl esters improve in rats cognitive and memory performances impaired by scopolamine treatment or lesions of the nucleus basalis of Meynert.
2004 Feb 19
Simultaneous analysis of esterase and transferase activities in cytosol proteins from the bovine retina by using microscale non-denaturing two-dimensional electrophoresis.
2004 Jan 14
Disclosure of a pro-apoptotic glyceraldehyde-3-phosphate dehydrogenase promoter: anti-dementia drugs depress its activation in apoptosis.
2004 May 14
In vitro inactivation of rat brain acetylcholinesterase by DSP-4 and its derivatives OS-21 and OS-23 and protective activity of tacrine (9-amino-1,2,3,4-tetrahydroacridine).
2005
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
Pharmacological characterization of orally active cholinesterase inhibitory activity of Prunus persica L. Batsch in rats.
2006
Dopamine and adenosine receptor interaction as basis for the treatment of Parkinson's disease.
2006 Oct 25
Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer's disease.
2007
Progress update: Pharmacological treatment of Alzheimer's disease.
2007
Long-term tetrahydroaminoacridine treatment and quantitative EEG in Alzheimer's disease.
2007
Current therapeutic options for Alzheimer's disease.
2007 Dec
Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics.
2007 Jun
Allosteric modulation of muscarinic acetylcholine receptors.
2007 Sep
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
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 protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats.
2008 Oct
Comparative effects of cationic triarylmethane, phenoxazine and phenothiazine dyes on horse serum butyrylcholinesterase.
2008 Oct 15
Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.
2009
The 5-choice continuous performance test: evidence for a translational test of vigilance for mice.
2009
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
Effects of zonisamide on c-Fos expression under conditions of tacrine-induced tremulous jaw movements in rats: a potential mechanism underlying its anti-parkinsonian tremor effect.
2009 Jan
Determination of basic azaarenes in aviation kerosene by solid-phase extraction and HPLC-fluorescence detection.
2009 Jun
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
An integrated approach to improved toxicity prediction for the safety assessment during preclinical drug development using Hep G2 cells.
2009 Jun 1
Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration.
2009 Nov
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
A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.
2010 Jan 18
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
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
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
TACRINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
TACRINAL
Brand 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 Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
NDF-RT N0000175723
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
WHO-VATC QN06DA01
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
NDF-RT N0000000177
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
NCI_THESAURUS C47792
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
LIVERTOX NBK547868
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
Code System Code Type Description
EPA CompTox
DTXSID1037272
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
CHEBI
45980
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
ChEMBL
CHEMBL95
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
PUBCHEM
1935
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
NCI_THESAURUS
C61961
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
MERCK INDEX
M10424
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY Merck Index
IUPHAR
6687
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
RXCUI
10318
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY RxNorm
ECHA (EC/EINECS)
206-291-2
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
EVMPD
SUB10796MIG
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
DAILYMED
4VX7YNB537
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
FDA UNII
4VX7YNB537
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
DRUG CENTRAL
2551
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
INN
800
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
CAS
321-64-2
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
MESH
D013619
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
WIKIPEDIA
TACRINE
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY
DRUG BANK
DB00382
Created by admin on Sun Dec 18 19:07:49 UTC 2022 , Edited by admin on Sun Dec 18 19:07:49 UTC 2022
PRIMARY