Tacrine Explained

Watchedfields:changed
Verifiedrevid:470476624
Iupac Name:1,2,3,4-Tetrahydroacridin-9-amine
Width:150
Width2:200
Tradename:Cognex
Pregnancy Au:C
Pregnancy Us:C
Legal Au:S4
Legal Br:C1
Legal Br Comment:[1]
Legal Uk:POM
Legal Us:Rx-only
Routes Of Administration:Oral, rectal
Bioavailability:2.4–36% (oral)
Protein Bound:55%
Metabolism:Hepatic (CYP1A2)
Elimination Half-Life:2–4 hours
Excretion:Renal
Iuphar Ligand:6687
Cas Number:321-64-2
Atc Prefix:N06
Atc Suffix:DA01
Drugbank:DB00382
Chemspiderid:1859
Unii:4VX7YNB537
Chebi:45980
Chembl:95
Pdb Ligand:THA
C:13
H:14
N:2
Melting Point:183
Boiling Point:358
Smiles:n1c3c(c(c2c1cccc2)N)CCCC3
Stdinchi: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)
Stdinchikey:YLJREFDVOIBQDA-UHFFFAOYSA-N

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

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

Very common (>10% incidence) adverse effects include
Common (1-10% incidence) adverse effects include
Uncommon/rare (<1% incidence) adverse effects include
Unknown incidence adverse effects include

Overdose

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.

Pharmacokinetics

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.[12]

External links

Notes and References

  1. Web site: Anvisa . Brazilian Health Regulatory Agency . 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. live . https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 . 2023-08-03 . 2023-08-16 . . pt-BR . 2023-04-04.
  2. Taraschenko OD, Barnes WG, Herrick-Davis K, Yokoyama Y, Boyd DL, Hough LB . Actions of tacrine and galanthamine on histamine-N-methyltransferase . Methods and Findings in Experimental and Clinical Pharmacology . 27 . 3 . 161–165 . April 2005 . 15834447 . 10.1358/mf.2005.27.3.890872 .
  3. US . 4816456 . Summers WK . 28 March 1989. Administration of monoamine acridines in cholinergic neuronal deficit states.
  4. 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-for research Furor . Wall Street Journal . 4 August 1987 . A-1 .
  5. Web site: Peacock D . New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis. . NM Bus Weekly . 25 March 2005 .
  6. 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 . 280 . 20 . 1777–1782 . November 1998 . 9842955 . 10.1001/jama.280.20.1777 .
  7. Book: Rang HP, Dale MM, Ritter JM, Moore PK . Pharmacology . 5th . Edinburgh . Churchill Livingstone . 2003. 978-0-443-07145-4. .
  8. Web site: tacrine (Discontinued) - Cognex . Medscape Reference. WebMD. 8 October 2013. 30 June 2019. https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070. dead.
  9. Web site: Tacrine . LiverTox . U.S. National Institutes of Health . https://web.archive.org/web/20190702153735/http://www.livertox.nih.gov/Tacrine.htm . 2019-07-02 .
  10. Book: Elks J, Ganellin CR . Dictionary of Drugs. 1990. 10.1007/978-1-4757-2085-3. 978-1-4757-2087-7.
  11. Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW . Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease . JAMA . 271 . 13 . 992–998 . April 1994 . 8139084 . 10.1001/jama.1994.03510370044030 .
  12. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.

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