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Clinical data
Trade namesCognex
  • AU: C
Routes of
Oral, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability2.4–36% (oral)
Protein binding55%
MetabolismHepatic (CYP1A2)
Elimination half-life2–4 hours
  • 1,2,3,4-Tetrahydroacridin-9-amine
CAS Number
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.005.721 Edit this at Wikidata
Chemical and physical data
Molar mass198.269 g·mol−1
3D model (JSmol)
Melting point183 °C (361 °F)
Boiling point358 °C (676 °F)
  • n1c3c(c(c2c1cccc2)N)CCCC3
  • 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) checkY

Tacrine is a centrally acting acetylcholinesterase inhibitor 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 in 1949. It also acts as a histamine N-methyltransferase inhibitor.[2]

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 in 1989.[3][4][5] 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.[6][7]

Tacrine has been discontinued in the US[8] in 2013, due to concerns over safety.[9]

Tacrine was also described as an analeptic agent used to promote mental alertness.[10]

Adverse Effects[edit]

Very common (>10% incidence) adverse effects include[8]
Common (1-10% incidence) adverse effects include[8][11]
  • Indigestion
  • Belching
  • Abdominal pain
  • Myalgia — muscle pain
  • Confusion
  • Ataxia — decreased control over bodily movements.
  • Insomnia
  • Rhinitis
  • Rash
  • Fatigue
  • Weight loss
  • Constipation
  • Somnolence
  • Tremor
  • Anxiety
  • Urinary incontinence
  • Hallucinations
  • Agitation
  • Conjunctivitis (a link to tacrine treatment has not been conclusively proven)
  • Diaphoresis — sweating.
Uncommon/rare (<1% incidence) adverse effects include[11]
  • Hepatotoxicity (that is toxic effects on the liver)
  • Ototoxicity (hearing/ear damage; a link to tacrine treatment has not been conclusively proven)
  • Seizures
  • Agranulocytosis (a link between treatment and this adverse effect has not been proven) — a potentially fatal drop in white blood cells, the body's immune/defensive cells.
  • Taste changes
Unknown incidence adverse effects include[11]


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.[11]


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.[11]


  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ 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.
  3. ^ US 4816456, Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", issued 28 March 1989 
  4. ^ Waldholz M (4 August 1987). 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-for research Furor. Wall Street Journal (Report). p. A-1.
  5. ^ Peacock D (25 March 2005). "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis". NM Bus Weekly.
  6. ^ Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M (November 1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA. 280 (20): 1777–1782. doi:10.1001/jama.280.20.1777. PMID 9842955.
  7. ^ Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4..
  8. ^ a b c "tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Archived from the original on 30 June 2019. Retrieved 8 October 2013.
  9. ^ "Tacrine". LiverTox. U.S. National Institutes of Health. Archived from the original on 2019-07-02.
  10. ^ Elks J, Ganellin CR, eds. (1990). Dictionary of Drugs. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7.
  11. ^ 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]