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Details

Stereochemistry ACHIRAL
Molecular Formula C13H14N2.ClH
Molecular Weight 234.725
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TACRINE HYDROCHLORIDE

SMILES

Cl.NC1=C2CCCCC2=NC3=C1C=CC=C3

InChI

InChIKey=ZUFVXZVXEJHHBN-UHFFFAOYSA-N
InChI=1S/C13H14N2.ClH/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);1H

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)
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
Ketamine-induced postanesthetic delirium attenuated by tetrahydroaminoacridine.
1974 Jul
Amino acridines action on Friend's retrovirus in relation to their molecular ionization.
1989
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
Tacrine, a reversible acetylcholinesterase inhibitor, induces myopathy.
2000 Apr 27
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine.
2001 Jan
Flumazenil and tacrine increase the effectiveness of ondansetron on scopolamine-induced impairment of spatial learning in rats.
2003 Aug
Reduction in distractibility with AF102B and THA in the macaque.
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
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
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
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
WITHDRAWN: Tacrine for Alzheimer's disease.
2007 Jul 18
Heterologous amyloid seeding: revisiting the role of acetylcholinesterase in Alzheimer's disease.
2007 Jul 25
Allosteric modulation of muscarinic acetylcholine receptors.
2007 Sep
The investigation of structure-activity relationships of tacrine analogues: electronic-topological method.
2008 Aug 6
A 5-HT2A receptor inverse agonist, ACP-103, reduces tremor in a rat model and levodopa-induced dyskinesias in a monkey model.
2008 Oct
Rapid determination of tacrine and other drug metabolites in microsomal incubate by newly developed targeting algorithm on UHPLC/TOFMS.
2009 Dec 15
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
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
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
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 HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
TACRINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
TACRINE HCL
Common Name English
NSC-72108
Code English
TACRINE HYDROCHLORIDE [MI]
Common Name English
Tacrine hydrochloride [WHO-DD]
Common Name English
COGNEX
Brand Name English
TACRINE HYDROCHLORIDE [USAN]
Common Name English
TACRINE HYDROCHLORIDE [VANDF]
Common Name English
9-ACRIDINAMINE, 1,2,3,4-TETRAHYDRO-, MONOHYDROCHLORIDE
Common Name English
9-Amino-1,2,3,4-tetrahydroacridine monohydrochloride
Systematic Name English
TACRINE HYDROCHLORIDE [MART.]
Common Name English
CI-970
Code English
TACRINE HYDROCHLORIDE [USP IMPURITY]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47792
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
Code System Code Type Description
CAS
1684-40-8
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY
PUBCHEM
2723754
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PRIMARY
ChEMBL
CHEMBL95
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY
NSC
72108
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY
FDA UNII
4966RNG0BU
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY
ECHA (EC/EINECS)
216-867-5
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PRIMARY
RXCUI
235972
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY RxNorm
EVMPD
SUB04665MIG
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PRIMARY
EPA CompTox
DTXSID1026112
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PRIMARY
USAN
AA-35
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PRIMARY
MERCK INDEX
m10424
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PRIMARY Merck Index
SMS_ID
100000084787
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PRIMARY
NCI_THESAURUS
C47742
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY
DRUG BANK
DBSALT001053
Created by admin on Fri Dec 15 15:10:50 GMT 2023 , Edited by admin on Fri Dec 15 15:10:50 GMT 2023
PRIMARY