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Details

Stereochemistry ACHIRAL
Molecular Formula C13H14N2.ClH.H2O
Molecular Weight 252.74
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TACRINE HYDROCHLORIDE MONOHYDRATE

SMILES

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

InChI

InChIKey=PXGRMZYJAOQPNZ-UHFFFAOYSA-N
InChI=1S/C13H14N2.ClH.H2O/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;1H2

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C13H14N2
Molecular Weight 198.2637
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
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
Severe parkinsonian symptom development on combination treatment with tacrine and haloperidol.
1995 Aug
Convulsive effects of tacrine.
1996 May 11
Tacrine, a reversible acetylcholinesterase inhibitor, induces myopathy.
2000 Apr 27
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
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
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
The evaluation of cognitive function in the dementias: methodological and regulatory considerations.
2003 Mar
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
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
[Study of the cholinesterase active site using a fluorescent probe].
2004 Mar-Apr
Disclosure of a pro-apoptotic glyceraldehyde-3-phosphate dehydrogenase promoter: anti-dementia drugs depress its activation in apoptosis.
2004 May 14
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
In vitro and in vivo characterization of F-97013-GD, a partial 5-HT1A agonist with antipsychotic- and antiparkinsonian-like properties.
2006 Jul
Current therapeutic options for Alzheimer's disease.
2007 Dec
Allosteric modulation of muscarinic acetylcholine receptors.
2007 Sep
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
Cholinesterase inhibitors for delirium.
2008 Jan 23
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
The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats.
2008 Oct
Comparison studies of tacrine and bis7-tacrine on the suppression of scopolamine-induced behavioral changes and inhibition of acetylcholinesterase in mice.
2009
Dual-acting drugs: an in vitro study of nonimidazole histamine H3 receptor antagonists combining anticholinesterase activity.
2010 Jul 5
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).
Substance Class Chemical
Created
by admin
on Thu Jul 06 11:36:18 UTC 2023
Edited
by admin
on Thu Jul 06 11:36:18 UTC 2023
Record UNII
MQ603P8SBL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TACRINE HYDROCHLORIDE MONOHYDRATE
Common Name English
9-ACRIDINAMINE, 1,2,3,4-TETRAHYDRO-, HYDROCHLORIDE, HYDRATE (1:1:1)
Systematic Name English
9-ACRIDINAMINE, 1,2,3,4-TETRAHYDRO-, MONOHYDROCHLORIDE, MONOHYDRATE
Common Name English
Code System Code Type Description
FDA UNII
MQ603P8SBL
Created by admin on Thu Jul 06 11:36:18 UTC 2023 , Edited by admin on Thu Jul 06 11:36:18 UTC 2023
PRIMARY
EPA CompTox
DTXSID80221711
Created by admin on Thu Jul 06 11:36:18 UTC 2023 , Edited by admin on Thu Jul 06 11:36:18 UTC 2023
PRIMARY
PUBCHEM
6420002
Created by admin on Thu Jul 06 11:36:18 UTC 2023 , Edited by admin on Thu Jul 06 11:36:18 UTC 2023
PRIMARY
CAS
7149-50-0
Created by admin on Thu Jul 06 11:36:18 UTC 2023 , Edited by admin on Thu Jul 06 11:36:18 UTC 2023
PRIMARY
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