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
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)
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
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 |
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 Date1993 |
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 |
|---|---|---|
| An appraisal of tacrine-extended suxamethonium. | 1970 Feb |
|
| Ketamine-induced postanesthetic delirium attenuated by tetrahydroaminoacridine. | 1974 Jul |
|
| Influence of tetrahydro-aminacrine on muscle pains after suxamethonium. | 1975 Jan 18 |
|
| Amino acridines action on Friend's retrovirus in relation to their molecular ionization. | 1989 |
|
| A comparison of the effects of cholinergic and dopaminergic agents on scopolamine-induced hyperactivity in mice. | 1990 Nov |
|
| Effects of four non-cholinergic cognitive enhancers in comparison with tacrine and galanthamine on scopolamine-induced amnesia in rats. | 1992 |
|
| Synthesis and cholinergic properties of bis[[(dimethylamino)methyl]furanyl] analogues of ranitidine. | 1992 Mar 20 |
|
| Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, tacrine and NIK-247 in rats. | 1993 Nov 30 |
|
| Tacrine, a reversible acetylcholinesterase inhibitor, induces myopathy. | 2000 Apr 27 |
|
| 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 |
|
| Neuronal overexpression of "readthrough" acetylcholinesterase is associated with antisense-suppressible behavioral impairments. | 2002 |
|
| Effects of acute nicotine administration on cognitive event-related potentials in tacrine-treated and non-treated patients with Alzheimer's disease. | 2002 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Evidence for the involvement of central serotonergic mechanisms in cholinergic tremor induced by tacrine in Balb/c mice. | 2005 Sep 8 |
|
2006 Jun |
||
| Potential cognitive enhancing and disease modification effects of SSRIs for Alzheimer's disease. | 2007 |
|
| 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 |
|
| 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 |
|
| The protective effect of the cholinergic anti-inflammatory pathway against septic shock in rats. | 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 |
|
| The 5-choice continuous performance test: evidence for a translational test of vigilance for mice. | 2009 |
|
| Rapid determination of tacrine and other drug metabolites in microsomal incubate by newly developed targeting algorithm on UHPLC/TOFMS. | 2009 Dec 15 |
|
| 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 |
|
| Synthesis and AChE inhibitory activity of new chiral tetrahydroacridine analogues from terpenic cyclanones. | 2010 Feb |
|
| 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 |
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
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WHO-ATC |
N06DA01
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NDF-RT |
N0000175723
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WHO-VATC |
QN06DA01
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NDF-RT |
N0000000177
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NCI_THESAURUS |
C47792
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LIVERTOX |
NBK547868
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DTXSID1037272
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45980
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CHEMBL95
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1935
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C61961
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m10424
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6687
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10318
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100000082994
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206-291-2
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SUB10796MIG
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4VX7YNB537
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2551
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800
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321-64-2
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D013619
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TACRINE
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DB00382
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE ACTIVE (PARENT)
SALT/SOLVATE (PARENT)
SALT/SOLVATE (PARENT)
