Tacrine

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Tacrine
Tacrine2DACS.svg
Tacrine3Dan.gif
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade namesCognex
AHFS/Drugs.commonograph
MedlinePlusa693039
Pregnancy cat.
Legal status
RoutesOral, rectal
Pharmacokinetic data
Bioavailability2.4–36% (oral)
Protein binding55%
MetabolismHepatic (CYP1A2)
Half-life2–4 hours
ExcretionRenal
Identifiers
CAS number321-64-2 YesY
ATC codeN06DA01
DrugBankDB00382
ChemSpider1859 YesY
UNII4VX7YNB537 YesY
ChEBICHEBI:45980 YesY
ChEMBLCHEMBL95 YesY
PDB ligand IDTHA (PDBe, RCSB PDB)
Chemical data
FormulaC13H14N2 
Mol. mass198.264 g/mol
Physical data
Melt. point183 °C (361 °F)
Boiling point358 °C (676 °F)
 YesY (what is this?)  (verify)
 
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Tacrine
Tacrine2DACS.svg
Tacrine3Dan.gif
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade namesCognex
AHFS/Drugs.commonograph
MedlinePlusa693039
Pregnancy cat.
Legal status
RoutesOral, rectal
Pharmacokinetic data
Bioavailability2.4–36% (oral)
Protein binding55%
MetabolismHepatic (CYP1A2)
Half-life2–4 hours
ExcretionRenal
Identifiers
CAS number321-64-2 YesY
ATC codeN06DA01
DrugBankDB00382
ChemSpider1859 YesY
UNII4VX7YNB537 YesY
ChEBICHEBI:45980 YesY
ChEMBLCHEMBL95 YesY
PDB ligand IDTHA (PDBe, RCSB PDB)
Chemical data
FormulaC13H14N2 
Mol. mass198.264 g/mol
Physical data
Melt. point183 °C (361 °F)
Boiling point358 °C (676 °F)
 YesY (what is this?)  (verify)

Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist (parasympathomimetic). It was the first centrally acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the University of Sydney. It also acts as a histamine N-methyltransferase inhibitor.[1]

Clinical use[edit]

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. William K. Summers received a patent for this use (US Patent No. 4,816,456).[2][3][4] 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.[5][6]

Tacrine has been discontinued in the US.[7]

Adverse Effects[edit]

Very Common (>10% incidence) adverse effects include[7]
Common (1-10% incidence) adverse effects include[7][8]
Uncommon/Rare (<1% incidence) adverse effects include[8]
Unknown incidence adverse effects include[8]

Overdose[edit]

As stated above, overdosage of tacrine may give rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Atropine is a popular treatment for overdose.[8]

Pharmacokinetics[edit]

Major form of metabolism is in the liver via hydroxylation of benzylic carbon by CYP1A2. This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.[8]

References[edit]

  1. ^ Taraschenko, OD; Barnes, WG; Herrick-Davis, K; Yokoyama, Y; Boyd, DL; Hough, LB (April 2005). "Actions of tacrine and galanthamine on histamine-N-methyltransferase.". Methods and findings in experimental and clinical pharmacology 27 (3): 161-165. doi:10.1358/mf.2005.27.3.890872. PMID 15834447. 
  2. ^ {US Patent No. 4,816,456} http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4,816,456.PN.&OS=PN/4,816,456&RS=PN/4,816,456
  3. ^ Waldholz M. A Psychiatrist’s work leads to a US study of Alzheimer’s drug: but Dr. Summers shuns test, seeks to widen his own; is Memory really aided; Fee-forresearch Furor. Wall Street Journal. Tuesday August 4, 1987 p A-1
  4. ^ Peacock D. New Mexico Doctor invents drugs, supplements for Alzheimer’s disease, Multiple Sclerosis. NM Bus Weekly. 25 MAR 2005
  5. ^ Qizilbash N, Whitehead A, Higgins J, et al. (1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials". Journal of the American Medical Association 280 (20): 1777–82. doi:10.1001/jama.280.20.1777. PMID 9842955. 
  6. ^ Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed. ed.). Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. .
  7. ^ a b c "tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Retrieved 8 October 2013. 
  8. ^ a b c d e Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.

External links[edit]

See also[edit]