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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2020-02-26 21:39:49 UTC
HMDB IDHMDB0014526
Secondary Accession Numbers
  • HMDB14526
Metabolite Identification
Common NameTacrine
DescriptionTacrine, also known as tacrinal or THA, 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. Taste changesUnknown incidence adverse effects includeUrinary tract infectionDeliriumOther optic effects such as glaucoma, cataracts, etc (also not conclusively linked to tacrine treatment)DepressionSuicidal ideation and behaviourHypotensionBradycardiaAs stated above, overdosage of tacrine may give rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Tacrine is a drug. Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist (parasympathomimetic). Atropine is a popular treatment for overdose. Tacrine is a very strong basic compound (based on its pKa). Very Common (>10% incidence) adverse effects includeIncreased LFTsNauseaVomitingDiarrheaHeadacheDizzinessCommon (1-10% incidence) adverse effects includeIndigestionBelchingAbdominal painMyalgia — muscle painConfusionAtaxia — decreased control over bodily movements. Tacrine is a potentially toxic compound. It also acts as a histamine N-methyltransferase inhibitor. It was the first centrally acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. William K. Summers received a patent for this use (US Patent No. 4,816,456). Tacrine has been discontinued in the US in 2013, due to concerns over safety. Major form of metabolism is in the liver via hydroxylation of benzylic carbon by CYP1A2. Tacrine was first synthesised by Adrien Albert at the University of Sydney. Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. Studies found that it may have a small beneficial effect on cognition and other clinical measures, though study data was limited and the clinical relevance of these findings was unclear.
Structure
Data?1582753189
Synonyms
ValueSource
1,2,3,4-Tetrahydro-9-acridinamineChEBI
1,2,3,4-Tetrahydro-9-aminoacridineChEBI
5-Amino-6,7,8,9-tetrahydroacridineChEBI
9-Amino-1,2,3,4-tetrahydroacridineChEBI
TetrahydroaminacrineChEBI
TacrinalKegg
TetrahydroaminoacridineHMDB
TetrahydroaminocrinHMDB
TetrahydroaminocrineHMDB
THAHMDB
1,2,3,4-TetrahydroaminoacridineHMDB
Horizon brand OF tacrine hydrochlorideHMDB
OTL pharm brand OF tacrine hydrochlorideHMDB
Parke davis brand OF tacrine hydrochlorideHMDB
TenakrinHMDB
RomotalHMDB
CognexHMDB
Tacrine hydrochlorideHMDB
Woods brand OF tacrine hydrochlorideHMDB
Chemical FormulaC13H14N2
Average Molecular Weight198.2637
Monoisotopic Molecular Weight198.115698458
IUPAC Name1,2,3,4-tetrahydroacridin-9-amine
Traditional Nametacrine
CAS Registry Number321-64-2
SMILES
NC1=C2CCCCC2=NC2=CC=CC=C12
InChI Identifier
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)
InChI KeyYLJREFDVOIBQDA-UHFFFAOYSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassBenzoquinolines
Direct ParentAcridines
Alternative Parents
Substituents
  • Acridine
  • 4-aminoquinoline
  • Aminoquinoline
  • Aminopyridine
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Azacycle
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point183.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.14 g/LNot Available
LogP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 g/LALOGPS
logP3.13ALOGPS
logP2.63ChemAxon
logS-3.2ALOGPS
pKa (Strongest Basic)8.95ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area38.91 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity61.74 m³·mol⁻¹ChemAxon
Polarizability22.79 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00r2-0900000000-e2921d2cb64d7c502a4bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-0900000000-453e4e963f034e9de4cfSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-0900000000-256a5702a96325bc74f2Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-0900000000-af483bfb98e7e2b87b39Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-006t-0900000000-3c9902ca237f9c26a2fbSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-006x-0900000000-dec59115a19fdec78a9fSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0900000000-c04cbf634e493a774cd5Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001j-0900000000-2f420836beda4ff3e6b2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-001i-0900000000-2275f7938116d06948a0Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-001i-2900000000-1f84e054a206191e525dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0900000000-e9e614ab5237139c5988Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-0900000000-0903202525aeeeca151cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00l2-0900000000-ba164ed659e5620dad0aSpectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00382 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00382 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00382
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID1859
KEGG Compound IDC01453
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTacrine
METLIN IDNot Available
PubChem Compound1935
PDB IDNot Available
ChEBI ID45980
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  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:9842955 ]
  2. Hansen RA, Gartlehner G, Kaufer DJ, Lohr KN, Carey T: [PubMed:20480924 ]

Enzymes

General function:
Involved in carboxylesterase 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
Molecular weight:
67795.525
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:10024872 ]
  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:10208549 ]
  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:10210906 ]
  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:10375753 ]
  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:10513568 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:16880719 ]
  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:15544504 ]
  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:17218977 ]
  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:15544507 ]
  11. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [PubMed:12871155 ]
  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:16860785 ]
General function:
Involved in carboxylesterase activity
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
Molecular weight:
68417.575
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:10375753 ]
  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:17218977 ]
  3. Marco JL, Carreiras MC: Recent developments in the synthesis of acetylcholinesterase inhibitors. Mini Rev Med Chem. 2003 Sep;3(6):518-24. [PubMed:12871155 ]
  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:16860785 ]
General function:
Involved in monooxygenase activity
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 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. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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:19754423 ]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  3. 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:12065442 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
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:12438524 ]