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
An appraisal of tacrine-extended suxamethonium.
1970 Feb
Correlation of brain levels of 9-amino-1,2,3,4-tetrahydroacridine (THA) with neurochemical and behavioral changes.
1989 Nov 28
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
Adverse interaction of tacrine and haloperidol.
1996 Nov
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.
2001 Jan
Ameliorative effects of azaindolizinone derivative ZSET845 on scopolamine-induced deficits in passive avoidance and radial-arm maze learning in the rat.
2001 Nov
Sleep-wake mechanisms and drug discovery: sleep EEG as a tool for the development of CNS-acting drugs.
2002 Dec
[Protective effects of tacrine and donepezil against staurosporine-induced apoptotic death].
2002 Feb
Effects of amphetamine on the plus-maze discriminative avoidance task in mice.
2002 Feb
Nicotine and sensory memory in Alzheimer's disease: an event-related potential study.
2002 Jul
Novel tacrine derivatives that block neuronal calcium channels.
2002 Jun
Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition.
2003 Apr
Inhibition of human cholinesterases by drugs used to treat Alzheimer disease.
2003 Apr-Jun
Selective 5-HT1A antagonists WAY 100635 and NAD-299 attenuate the impairment of passive avoidance caused by scopolamine in the rat.
2003 Feb
Assessment of hepatocytes and liver slices as in vitro test systems to predict in vivo gene expression.
2003 Sep
Inhibition of murine cytochrome P4501A by tacrine: in vitro studies.
2004 Aug
Cholinesterase inhibitors modify the activity of intrinsic cardiac neurons.
2004 Aug
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
Cholinergic drugs potentiate human nicotinic alpha4beta2 acetylcholine receptors by a competitive mechanism.
2005 Feb 21
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
Allosteric modulation of muscarinic acetylcholine receptors.
2007 Sep
Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats.
2008 Jan
New performance of biosensor technology for Alzheimer's disease drugs: in vitro comparison of tacrine and 7-methoxytacrine.
2008 Oct
A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model.
2008 Oct
Study of neuroprotection of donepezil, a therapy for Alzheimer's disease.
2008 Sep 25
Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in 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
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
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
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
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
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 Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
NDF-RT N0000175723
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
WHO-VATC QN06DA01
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
NDF-RT N0000000177
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
NCI_THESAURUS C47792
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
LIVERTOX NBK547868
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID1037272
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
CHEBI
45980
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
ChEMBL
CHEMBL95
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
PUBCHEM
1935
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
NCI_THESAURUS
C61961
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
MERCK INDEX
M10424
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY Merck Index
IUPHAR
6687
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
RXCUI
10318
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY RxNorm
SMS_ID
100000082994
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
ECHA (EC/EINECS)
206-291-2
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
EVMPD
SUB10796MIG
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
FDA UNII
4VX7YNB537
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
DRUG CENTRAL
2551
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
INN
800
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
CAS
321-64-2
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
MESH
D013619
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
WIKIPEDIA
TACRINE
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY
DRUG BANK
DB00382
Created by admin on Thu Jul 06 22:12:36 UTC 2023 , Edited by admin on Thu Jul 06 22:12:36 UTC 2023
PRIMARY