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Details

Stereochemistry ACHIRAL
Molecular Formula C13H14N2
Molecular Weight 198.2641
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TACRINE

SMILES

c1ccc2c(c1)c(=N)c3CCCCc3[nH]2

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

Molecular Formula C13H14N2
Molecular Weight 198.2641
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
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
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
Sleep-wake mechanisms and drug discovery: sleep EEG as a tool for the development of CNS-acting drugs.
2002 Dec
The evaluation of cognitive function in the dementias: methodological and regulatory considerations.
2003 Mar
2006 Jun
Progress update: Pharmacological treatment of Alzheimer's disease.
2007
Heterologous amyloid seeding: revisiting the role of acetylcholinesterase in Alzheimer's disease.
2007 Jul 25
Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics.
2007 Jun
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity.
2008 Dec 25
Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors.
2008 Jun 12
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
A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model.
2008 Oct
Comparative effects of cationic triarylmethane, phenoxazine and phenothiazine dyes on horse serum butyrylcholinesterase.
2008 Oct 15
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
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
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
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
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).
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:25:43 UTC 2021
Edited
by admin
on Fri Jun 25 23:25:43 UTC 2021
Record UNII
4VX7YNB537
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TACRINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
TACRINE [WHO-DD]
Common Name English
TACRINAL
Brand 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 Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
NDF-RT N0000175723
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
WHO-VATC QN06DA01
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
NDF-RT N0000000177
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
NCI_THESAURUS C47792
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
LIVERTOX 918
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
Code System Code Type Description
EPA CompTox
321-64-2
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL95
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
PUBCHEM
1935
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
NCI_THESAURUS
C61961
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
MERCK INDEX
M10424
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY Merck Index
IUPHAR
6687
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
RXCUI
10318
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
206-291-2
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
EVMPD
SUB10796MIG
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
FDA UNII
4VX7YNB537
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
DRUG CENTRAL
2551
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
INN
800
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
CAS
321-64-2
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
MESH
D013619
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
WIKIPEDIA
TACRINE
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
DRUG BANK
DB00382
Created by admin on Fri Jun 25 23:25:43 UTC 2021 , Edited by admin on Fri Jun 25 23:25:43 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
URINE
METABOLITE -> PARENT
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC