Identification
- Summary
Tacrine is an anticholinesterase drug used for the management of Alzheimer's disease symptoms.
- Generic Name
- Tacrine
- DrugBank Accession Number
- DB00382
- Background
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. Tacrine has been discontinued for the United States market.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Tacrine (DB00382)
- Weight
- Average: 198.2637
Monoisotopic: 198.115698458 - Chemical Formula
- C13H14N2
- Synonyms
- 1,2,3,4-tetrahydro-9-acridinamine
- 1,2,3,4-tetrahydro-9-aminoacridine
- 1,2,3,4-tetrahydroacridin-9-amine
- 5-amino-6,7,8,9-tetrahydroacridine
- 9-amino-1,2,3,4-tetrahydroacridine
- Tacrin
- Tacrine
- Tacrinum
- Tetrahydroaminacrine
- Tetrahydroaminoacridine
- THA
- External IDs
- CI 970
Pharmacology
- Indication
For the palliative treatment of mild to moderate dementia of the Alzheimer's type.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ACholinesterase inhibitorHumans AAcetylcholinesterase inhibitorHumans ULiver carboxylesterase 1 Not Available Humans - 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.
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- Route of elimination
Not Available
- Half-life
2 to 4 hours
- Clearance
Not Available
- Adverse Effects
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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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Tacrine can be increased when it is combined with Abametapir. Abatacept The metabolism of Tacrine can be increased when combined with Abatacept. Abiraterone The serum concentration of Tacrine can be increased when it is combined with Abiraterone. Acebutolol Tacrine may increase the bradycardic activities of Acebutolol. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Tacrine. - Food Interactions
- Take on an empty stomach. Take tacrine at least one hour before meals for optimal absorption.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Tacrine Hydrochloride 4966RNG0BU 1684-40-8 ZUFVXZVXEJHHBN-UHFFFAOYSA-N - International/Other Brands
- Talem (LKM)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Cognex Capsule 30 mg/1 Oral Shionogi 1993-09-09 2010-09-30 US 
Cognex Capsule 40 mg/1 Oral Shionogi 1993-09-09 2010-09-30 US Cognex Capsule 20 mg/1 Oral Shionogi 1993-09-09 2010-09-30 US Cognex Capsule 10 mg/1 Oral Shionogi 1993-09-09 2010-09-30 US
Categories
- ATC Codes
- N06DA01 — Tacrine
- Drug Categories
- Acridines
- Agents Causing Muscle Toxicity
- Aminoacridines
- Anti-Dementia Drugs
- Autonomic Agents
- Central Nervous System Agents
- Cholinergic Agents
- Cholinesterase Inhibitors
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 Substrates
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Nervous System
- Neurotransmitter Agents
- Nootropic Agents
- P-glycoprotein substrates
- Parasympathomimetics
- Peripheral Nervous System Agents
- Psychoanaleptics
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Benzoquinolines
- Direct Parent
- Acridines
- Alternative Parents
- 4-aminoquinolines / Aminopyridines and derivatives / Benzenoids / Heteroaromatic compounds / Azacyclic compounds / Primary amines / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 4-aminoquinoline / Acridine / Amine / Aminopyridine / Aminoquinoline / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Heteroaromatic compound / Hydrocarbon derivative
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic amine, acridines (CHEBI:45980) / a small molecule (CPD-10887)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 4VX7YNB537
- CAS number
- 321-64-2
- InChI Key
- 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)
- IUPAC Name
- 1,2,3,4-tetrahydroacridin-9-amine
- SMILES
- NC1=C2CCCCC2=NC2=CC=CC=C12
References
- Synthesis Reference
S. Shirley Yang, Wayne Boisvert, Nouman A. Muhammad, Jay Weiss, "Controlled release tacrine drug delivery systems and methods for preparing same." U.S. Patent US5576022, issued February, 1993.
US5576022- General References
- 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. [Article]
- Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: Drug Class Review: Alzheimer's Drugs: Final Report [Internet] . [Article]
- External Links
- Human Metabolome Database
- HMDB0014526
- KEGG Drug
- D08555
- KEGG Compound
- C01453
- PubChem Compound
- 1935
- PubChem Substance
- 46505487
- ChemSpider
- 1859
- BindingDB
- 8961
- 10318
- ChEBI
- 45980
- ChEMBL
- CHEMBL95
- ZINC
- ZINC000019014866
- Therapeutic Targets Database
- DAP000558
- PharmGKB
- PA451576
- PDBe Ligand
- THA
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Tacrine
- PDB Entries
- 1acj / 1mx1 / 2aow / 2aox / 4bds / 7xn1 / 8t5g
- MSDS
- Download (19.4 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Withdrawn Treatment Dependence, Cocaine 1
Pharmacoeconomics
- Manufacturers
- Shionogi pharma inc
- Packagers
- Sciele Pharma Inc.
- West-Ward Pharmaceuticals
- Dosage Forms
Form Route Strength Capsule Oral 10 mg/1 Capsule Oral 20 mg/1 Capsule Oral 30 mg/1 Capsule Oral 40 mg/1 - Prices
Unit description Cost Unit Cognex 10 mg capsule 3.03USD capsule Cognex 20 mg capsule 3.03USD capsule Cognex 40 mg capsule 3.03USD 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 (°C) 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 0.136 mg/mL 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 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 61.74 m3·mol-1 Chemaxon Polarizability 22.79 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9783 Blood Brain Barrier + 0.978 Caco-2 permeable - 0.5267 P-glycoprotein substrate Non-substrate 0.6195 P-glycoprotein inhibitor I Non-inhibitor 0.9247 P-glycoprotein inhibitor II Non-inhibitor 0.9103 Renal organic cation transporter Non-inhibitor 0.5073 CYP450 2C9 substrate Non-substrate 0.8532 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.7248 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5541 Ames test AMES toxic 0.9107 Carcinogenicity Non-carcinogens 0.9404 Biodegradation Not ready biodegradable 0.9773 Rat acute toxicity 3.4207 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9351 hERG inhibition (predictor II) Non-inhibitor 0.6164
Spectra
- Mass Spec (NIST)
- Download (9.22 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 148.8209875 predictedDarkChem Lite v0.1.0 [M-H]- 141.4167958 predictedDarkChem Lite v0.1.0 [M-H]- 141.28316 predictedDeepCCS 1.0 (2019) [M+H]+ 148.8012875 predictedDarkChem Lite v0.1.0 [M+H]+ 145.176169 predictedDarkChem Lite v0.1.0 [M+H]+ 144.1693 predictedDeepCCS 1.0 (2019) [M+Na]+ 149.2992875 predictedDarkChem Lite v0.1.0 [M+Na]+ 149.0541875 predictedDarkChem Lite v0.1.0 [M+Na]+ 153.51646 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Identical protein binding
- Specific Function
- Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
- Gene Name
- BCHE
- Uniprot ID
- P06276
- Uniprot Name
- Cholinesterase
- Molecular Weight
- 68417.575 Da
References
- 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. [Article]
- 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. [Article]
- Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serine hydrolase activity
- Specific Function
- Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
- Gene Name
- ACHE
- Uniprot ID
- P22303
- Uniprot Name
- Acetylcholinesterase
- Molecular Weight
- 67795.525 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Triglyceride lipase activity
- Specific Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
- Gene Name
- CES1
- Uniprot ID
- P23141
- Uniprot Name
- Liver carboxylesterase 1
- Molecular Weight
- 62520.62 Da
References
- Bencharit S, Morton CL, Hyatt JL, Kuhn P, Danks MK, Potter PM, Redinbo MR: Crystal structure of human carboxylesterase 1 complexed with the Alzheimer's drug tacrine: from binding promiscuity to selective inhibition. Chem Biol. 2003 Apr;10(4):341-9. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- 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 un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- 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. [Article]
- 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. [Article]
- Flockhart Table of Drug Interactions [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
References
- Mohamed LA, Kaddoumi A: Tacrine sinusoidal uptake and biliary excretion in sandwich-cultured primary rat hepatocytes. J Pharm Pharm Sci. 2014;17(3):427-38. [Article]
Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 07:00