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
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
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 |
DescriptionSources: http://www.drugbank.ca/drugs/DB00382Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/cognex.html
Sources: http://www.drugbank.ca/drugs/DB00382
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.
CNS Activity
Originator
Sources: http://www.alzforum.org/therapeutics/tacrine
Curator's Comment: Originally developed by Warner-Lambert Co.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL220 Sources: http://www.drugbank.ca/drugs/DB00382 |
500.0 nM [IC50] | ||
Target ID: CHEMBL1914 Sources: http://www.drugbank.ca/drugs/DB00382 |
23.0 nM [IC50] | ||
Target ID: CHEMBL2190 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15834447 |
0.46 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Cognex Approved UseCognex® (tacrine hydrochloride capsules) is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. Launch Date7.474464E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7836549 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
91.8 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7836549 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.8 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7836549 |
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
Dose | Population | Adverse 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) Sources: Vomiting (21 patient) Anorexia (21 patient) Dyspepsia (21 patient) Diarrhea (21 patient) Abdominal pain (21 patient) |
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) Sources: Page: p. 5Atrial fibrillation (1 patient) Dyspnea (1 patient) Chest pain (1 patient) |
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) Sources: Page: p. 5Nausea (1 patient) Vomiting (1 patient) Pallor (1 patient) Vasodilatation (1 patient) Sweating increased (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
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 |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15834447
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
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Record UNII |
MQ603P8SBL
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Record Status |
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