Tacrine

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. William K. Summers received a patent for this use in 1989.{{cite patent | country = US | number = 4816456 | inventor = Summers WK | gdate = 28 March 1989| title = Administration of monoamine acridines in cholinergic neuronal deficit states}}{{cite report | vauthors = Waldholz M | title = 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 | work = Wall Street Journal | date = 4 August 1987 | page = A-1 }}{{cite web | vauthors = Peacock D | title = New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis. | work = NM Bus Weekly | date = 25 March 2005 | url = https://www.bizjournals.com/albuquerque/stories/2005/03/28/smallb2.html }} 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.{{cite journal | vauthors = Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M | title = Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration | journal = JAMA | volume = 280 | issue = 20 | pages = 1777–1782 | date = November 1998 | pmid = 9842955 | doi = 10.1001/jama.280.20.1777 }}{{cite book |vauthors=Rang HP, Dale MM, Ritter JM, Moore PK |title=Pharmacology |edition=5th |location=Edinburgh |publisher=Churchill Livingstone |year=2003|isbn=978-0-443-07145-4}}.

Tacrine has been discontinued in the US{{cite web |title=tacrine (Discontinued) - Cognex |url= http://reference.medscape.com/drug/tacrine-343070 |work=Medscape Reference|publisher=WebMD|access-date=8 October 2013|archive-date=30 June 2019|archive-url=https://web.archive.org/web/20190630162718/https://reference.medscape.com/drug/tacrine-343070|url-status=dead}} in 2013, due to concerns over safety.{{cite web | url = http://www.livertox.nih.gov/Tacrine.htm | title = Tacrine | work = LiverTox | publisher = U.S. National Institutes of Health | archive-url = https://web.archive.org/web/20190702153735/http://www.livertox.nih.gov/Tacrine.htm | archive-date = 2019-07-02 }}

Tacrine was also described as an analeptic agent used to promote mental alertness.{{cite book| veditors = Elks J, Ganellin CR |title=Dictionary of Drugs|year=1990|doi=10.1007/978-1-4757-2085-3|isbn=978-1-4757-2087-7}}

;Very common (>10% incidence) adverse effects include

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• Increased liver function tests (LFT), with 49% of patients displaying elevated ALA{{cite journal | vauthors = Watkins PB, Zimmerman HJ, Knapp MJ, Gracon SI, Lewis KW | title = Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease | journal = JAMA | volume = 271 | issue = 13 | pages = 992–998 | date = April 1994 | pmid = 8139084 | doi = 10.1001/jama.1994.03510370044030 }}
• Diarrhea
• Dizziness
• Headache
• Nausea
• Vomiting

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;Common (1-10% incidence) adverse effects include

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• Abdominal pain
• Agitation
• Anxiety
• Ataxia — decreased control over bodily movements.
• Belching
• Confusion
• Conjunctivitis (a link to tacrine treatment has not been conclusively proven)
• Constipation
• Diaphoresis — sweating.
• Fatigue
• Hallucinations
• Indigestion
• Insomnia
• Myalgia — muscle pain
• Rash
• Rhinitis
• Somnolence
• Tremor
• Urinary incontinence
• Weight loss

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;Uncommon/rare (<1% incidence) adverse effects include

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• 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.
• Hepatotoxicity (that is toxic effects on the liver)
• Ototoxicity (hearing/ear damage; a link to tacrine treatment has not been conclusively proven)
• Seizures
• Taste changes

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;Unknown incidence adverse effects include

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• Bradycardia
• Delirium
• Depression
• Hypotension
• Suicidal ideation and behaviour
• Urinary tract infection
• Other optic effects such as glaucoma, cataracts, etc. (also not conclusively linked to tacrine treatment)

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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.

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.Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.

{{reflist}}

• [http://www.ebi.ac.uk/pdbe/quips?story=AChE Acetylcholinesterase: A gorge-ous enzyme] QUite Interesting PDB Structure article at [http://www.pdbe.org PDBe]

{{Anti-dementia drugs}}

{{Acetylcholine metabolism and transport modulators}}

{{Monoamine metabolism modulators}}

Category:Acetylcholinesterase inhibitors

Category:Antidementia agents