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Identification
Name Tacrine
Accession Number DB00382 (APRD00690)
Type small molecule
Groups approved
Description

A centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer’s disease and other central nervous system disorders. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Tetrahydroaminacrine
Tetrahydroaminoacridine
Tetrahydroaminocrin
Tetrahydroaminocrine
THA
Salts Not Available
Brand names
Name Company
Cognex
Romotal
Brand mixtures Not Available
Categories
  • Parasympathomimetics
  • Cholinesterase Inhibitors
  • Nootropic Agents
CAS number 321-64-2
Weight Average: 198.2637
Monoisotopic: 198.115698458
Chemical Formula C13H14N2
InChI Key InChIKey=YLJREFDVOIBQDA-UHFFFAOYSA-N
InChI
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)
Plain Text
IUPAC Name
1,2,3,4-tetrahydroacridin-9-amine
SMILES
NC1=C2CCCCC2=NC2=CC=CC=C12
Plain Text
Mass Spec show (9.22 KB)
Taxonomy
Kingdom Organic
Classes
  • Acridines
Substructures
  • Acridines
  • Pyridines and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aminoquinolines and Derivatives
  • Aminopyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Imines
  • Cyclohexenes and Derivatives
Pharmacology
Indication For the palliative treatment of mild to moderate dementia of the Alzheimer's type.
Pharmacodynamics 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.
Mechanism of action 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.
Absorption Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17%.
Volume of distribution
  • 349 ± 193 L
Protein binding 55%
Metabolism
Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Tacrine
1-hydroxytacrine Details
Route of elimination Not Available
Half life 2 to 4 hours
Clearance Not Available
Toxicity Overdosage with cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. The estimated median lethal dose of tacrine following a single oral dose in rats is 40 mg/kg, or approximately 12 times the maximum recommended human dose of 160 mg/day.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Shionogi pharma inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Cognex 10 mg capsule 3.03 USD capsule
Cognex 20 mg capsule 3.03 USD capsule
Cognex 40 mg capsule 3.03 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 183.5 °C PhysProp
water solubility 217 mg/L Not Available
logP 2.71 HANSCH,C ET AL. (1995)
pKa 9.95 (at 20 °C) PERRIN,DD (1972)
Predicted Properties
Property Value Source
water solubility 1.36e-01 g/l ALOGPS
logP 3.13 ALOGPS
logP 2.63 ChemAxon
logS -3.2 ALOGPS
pKa (strongest basic) 8.95 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 38.91 ChemAxon
rotatable bond count 0 ChemAxon
refractivity 61.74 ChemAxon
polarizability 22.79 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M: Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists’ Collaboration. JAMA. 1998 Nov 25;280(20):1777-82. Pubmed
  2. Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: Pubmed
External Links
Resource Link
KEGG Compound C01453 Link_out
PubChem Compound 1935 Link_out
PubChem Substance 46505487 Link_out
ChemSpider 1859 Link_out
BindingDB 8961 Link_out
ChEBI 9389 Link_out
ChEMBL 9389 Link_out
Therapeutic Targets Database DAP000558 Link_out
PharmGKB PA451576 Link_out
HET 760 Link_out
RxList http://www.rxlist.com/cgi/generic2/tacrine.htm Link_out
Drugs.com http://www.drugs.com/cdi/tacrine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Tacrine Link_out
ATC Codes
  • N06AA18
  • N06DA01
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (19.4 KB)
Interactions
Drug Interactions
Drug Interaction
Acetophenazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Acetophenazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Acetylcholine The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Acetylcholine, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Ambenonium The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Ambenonium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Aminophylline Tacrine may reduce the elimination rate of Aminophylline. Monitor for changes in the therapeutic and toxic effects of theophylline if Tacrine is initiated, discontinued or if the dose is changed.
Amitriptyline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amitriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Amlodipine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Amlopidine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Amlopidine is initiated, discontinued or if the dose is changed.
Amoxapine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Amoxapine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Aripiprazole Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Aripiprazole. Monitor for extrapyramidal symptoms.
Atropine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Atropine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Azelastine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Azelastine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Bendamustine CYP1A2 metabolism may result in increased levels of active metabolites, decreases levels of bendamustine.
Benzatropine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Benztropine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Betamethasone Tacrine and Betamethasone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Bethanechol The acetylcholinesterase inhibitor, Tacrine, may increase the cholinergic effects of Bethanecol, a cholinergic agonist. Monitor for increased cholinergic effects.
Biperiden The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Biperidin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Bromodiphenhydramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Bromodiphenhydramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Brompheniramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Brompheniramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Carbachol The acetylcholinesterase inhibitor, Tacrine, may increase the cholinergic effects of Carbachol, a cholinergic agonist. Monitor for increased cholinergic effects.
Carbinoxamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Carbinoxamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Cevimeline The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Cevimeline, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Chlorpheniramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Chlorpheniramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Chlorpromazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Chlorpromazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Cimetidine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Cimetidine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Cimetidine is initiated, discontinued or if the dose is changed.
Ciprofloxacin The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Ciprofloxacin. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Ciprofloxacin is initiated, discontinued or if the dose is changed.
Clemastine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clemastine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Clidinium The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clidinium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Clomipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Clozapine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Clozapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Corticotropin Tacrine and Corticotropin may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Cortisone acetate Tacrine and Cortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Cyclizine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyclizine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Cyclobenzaprine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyclobenzaprine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Cyclopentolate The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyclopentolate, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Cyproheptadine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Cyproheptadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Darifenacin The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Darifenacin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Demecarium The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Demcarium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Desipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Desipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Desloratadine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Desloratadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Dexamethasone Tacrine and Dexamethasone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Dexbrompheniramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Dexbrompheniramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Diclofenac The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Diclofenac, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Diclofenac is initiated, discontinued or if the dose is changed.
Dicyclomine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Dicyclomine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Dimenhydrinate The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Dimenhydrinate, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Diphenhydramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Diphenhydramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Doxepin The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxepin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Doxylamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Doxylamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Droperidol The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Droperidol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Edrophonium The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Edrophonium, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Fexofenadine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Fexofenadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Flavoxate The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Flavoxate, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Fludrocortisone Tacrine and Fludrocortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Fluoxetine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Fluoxetine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Fluoxetine is initiated, discontinued or if the dose is changed.
Flupenthixol The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Flupenthixol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Fluphenazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Fluphenazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Fluvoxamine Fluvoxamine, a strong CYP1A2 inhibitor, may decrease the metabolism and clearance of tacrine, a CYP1A2 substrate. Concomitant therapy should be avoided as it could lead to severe toxic effects such as hepatotoxicity. If concomitant therapy is used, monitor for altered efficacy and toxic effects, such as gastrointestinal and hepatic effects, of tacrine.
Gemfibrozil The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Gemfibrozil, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Gemfibrozil is initiated, discontinued or if the dose is changed.
Ginkgo biloba Ginkgo biloba may cause additive/toxic cholinergic effects when administered with Tacrine. Monitor for cholinergic toxicity.
Glycopyrrolate The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Glycopyrrolate, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Guanidine The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Guanidine, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Haloperidol The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Haloperidol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Homatropine Methylbromide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Homatropine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Hydrocortisone Tacrine and Hydrocortisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Hydroxyzine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Hydroxyzine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Hyoscyamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Hyoscyamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Imipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Imipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Ipratropium bromide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Ipratropium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Isocarboxazid The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Isocarboxazid, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Ketoconazole The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Ketoconazole. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Ketoconazole is initiated, discontinued or if the dose is changed.
Ketotifen The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Ketotifen, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Lidocaine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Lidocaine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Lidocaine is initiated, discontinued or if the dose is changed.
Loratadine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Loratadine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Loxapine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Loxapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Maprotiline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Maprotiline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Meclizine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Meclizine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Mepenzolate The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Mepenzolate, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Mesoridazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Mesoridazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Methantheline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Methantheline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Methoxsalen The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Methoxsalen. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Methoxsalen is initiated, discontinued or if the dose is changed.
Methylprednisolone Tacrine and Methylprednisolone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Methylscopolamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Methylscopolamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Mexiletine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Mexiletine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Mexiletine is initiated, discontinued or if the dose is changed.
Miconazole The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Miconazole, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Miconazole is initiated, discontinued or if the dose is changed.
Moclobemide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Moclobemide, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Molindone The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Molindone, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Nifedipine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Nifedipine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Nifedipine is initiated, discontinued or if the dose is changed.
Norfloxacin The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Norfloxacin. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Norfloxacin is initiated, discontinued or if the dose is changed.
Nortriptyline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Nortriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Ofloxacin The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Ofloxacin. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Ofloxacin is initiated, discontinued or if the dose is changed.
Olanzapine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Olanzapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Orphenadrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Orphenadrine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Oxtriphylline Tacrine increases the effect and toxicity of theophylline
Oxybutynin The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Oxybutynin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Paliperidone Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Paliperidone. Monitor for extrapyramidal symptoms.
Perphenazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Perphenazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Phenelzine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Phenelzine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Phenindamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Phenindamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Pilocarpine The acetylcholinesterase inhibitor, Tacrine, may increase the adverse/toxic effects of Pilocarpine, a cholinergic agonist. Monitor for increased cholinergic effects and toxicity.
Pimozide The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Pimozide, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Pizotifen The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Pizotifen, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Prednisolone Tacrine and Prednisolone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Prednisone Tacrine and Prednisone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Primaquine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Primaquine. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Primaquine is initiated, discontinued or if the dose is changed.
Prochlorperazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Prochlorperazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Procyclidine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Procyclidine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Promethazine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Promethazine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Propantheline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Propantheline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Propofol The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Propofol, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Propofol is initiated, discontinued or if the dose is changed.
Protriptyline The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Protriptyline, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Quetiapine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Quetiapine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Ramelteon Tacrine increases levels/toxicity of ramelteon
Risperidone The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Risperidone, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Scopolamine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Scopolamine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Solifenacin The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Solifenacin, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Succinylcholine Tacrine may increase the effects of Succinylcholine. Monitor Succinylcholine therapy for increased effects.
Theophylline Tacrine may reduce the elimination rate of Theophylline. Monitor for changes in the therapeutic and toxic effects of theophylline if Tacrine is initiated, discontinued or if the dose is changed.
Thiabendazole The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by strong CYP1A2 inhibitors such as Thiabendazole. Consider modifying therapy to avoid Tacrine toxicity. Monitor the efficacy and toxicity of Tacrine if Thiabendazole is initiated, discontinued or if the dose is changed.
Thioridazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Thioridazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Thiothixene The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Thiothixene, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Tiotropium The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Tiotropium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Tolterodine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Tolterodine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Tranylcypromine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Tranylcypromine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Tranylcypromine, a CYP1A2 inhibitor. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Triamcinolone Tacrine and Triamcinolone may independently exacerbate muscle weakness in myasthenia gravis patients. Monitor for additive muscle weakness effects.
Trifluoperazine The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Trifluoperazine, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Trihexyphenidyl The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trihexyphenidyl, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Trimeprazine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trimeprazine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Trimethobenzamide The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trimethobenzamide, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Trimipramine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trimipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Triprolidine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Triprolidine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Trospium The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Trospium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Ziprasidone Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Ziprasidone. Monitor for extrapyramidal symptoms.
Zuclopenthixol The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Zuclopenthixol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.
Food Interactions Not Available
Targets

1. Acetylcholinesterase

Pharmacological action: yes
Actions: inhibitor

Rapidly hydrolyzes choline released into the synapse

Organism class: human
UniProt ID: P22303 Link_out
Gene: ACHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Davis KL: Alzheimer’s disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington. Geriatrics. 1999 Feb;54(2):42-7; quiz 48. Pubmed
  2. Wang H, Carlier PR, Ho WL, Wu DC, Lee NT, Li CP, Pang YP, Han YF: Effects of bis(7)-tacrine, a novel anti-Alzheimer’s agent, on rat brain AChE. Neuroreport. 1999 Mar 17;10(4):789-93. Pubmed
  3. Traykov L, Tavitian B, Jobert A, Boller F, Forette F, Crouzel C, Di Giamberardino L, Pappata S: In vivo PET study of cerebral [11C] methyl- tetrahydroaminoacridine distribution and kinetics in healthy human subjects. Eur J Neurol. 1999 May;6(3):273-8. Pubmed
  4. Wang H, Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):27-30. Pubmed
  5. Kosasa T, Kuriya Y, Matsui K, Yamanishi Y: Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol. 1999 Sep 10;380(2-3):101-7. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Takatori Y: [Mechanisms of neuroprotective effects of therapeutic acetylcholinesterase inhibitors used in treatment of Alzheimer’s disease] Yakugaku Zasshi. 2006 Aug;126(8):607-16. Pubmed
  8. Du DM, Carlier PR: Development of bivalent acetylcholinesterase inhibitors as potential therapeutic drugs for Alzheimer’s disease. Curr Pharm Des. 2004;10(25):3141-56. Pubmed
  9. Krustev AD, Argirova MD, Getova DP, Turiiski VI, Prissadova NA: Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles. Can J Physiol Pharmacol. 2006 Nov;84(11):1133-8. Pubmed
  10. Villarroya M, Garcia AG, Marco JL: New classes of AChE inhibitors with additional pharmacological effects of interest for the treatment of Alzheimer’s disease. Curr Pharm Des. 2004;10(25):3177-84. Pubmed
  11. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. Pubmed
  12. Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morsch AL, Morsch VM, Schetinger MR: Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71. Epub 2006 Jun 17. Pubmed

2. Cholinesterase

Pharmacological action: yes
Actions: inhibitor

An acylcholine + H(2)O = choline + a carboxylate

Organism class: human
UniProt ID: P06276 Link_out
Gene: BCHE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang H, Tang XC: Anticholinesterase effects of huperzine A, E2020, and tacrine in rats. Zhongguo Yao Li Xue Bao. 1998 Jan;19(1):27-30. Pubmed
  2. Krustev AD, Argirova MD, Getova DP, Turiiski VI, Prissadova NA: Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth muscles. Can J Physiol Pharmacol. 2006 Nov;84(11):1133-8. Pubmed
  3. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. Pubmed
  4. Ahmed M, Rocha JB, Correa M, Mazzanti CM, Zanin RF, Morsch AL, Morsch VM, Schetinger MR: Inhibition of two different cholinesterases by tacrine. Chem Biol Interact. 2006 Aug 25;162(2):165-71. Epub 2006 Jun 17. Pubmed
Enzymes

1. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang B, Zhou SF: Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem. 2009;16(31):4066-218. Pubmed
  2. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  4. Obach RS, Reed-Hagen AE: Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metab Dispos. 2002 Jul;30(7):831-7. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19