Editing Tacrine

{{short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| Watchedfields = changed
| verifiedrevid = 470476624
| IUPAC_name = 1,2,3,4-Tetrahydroacridin-9-amine
| image = Tacrine2DACS.svg
| image_class = skin-invert-image
| width = 150
| image2 = Tacrine3Dan.gif
| width2 = 200
<!--Clinical data-->
| tradename = Cognex
| Drugs.com = {{drugs.com|monograph|tacrine-hydrochloride}}
| MedlinePlus = a693039
| pregnancy_AU = C
| pregnancy_US = C
| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=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 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=2023-04-04}}</ref>
| legal_UK = POM
| legal_US = Rx-only
| routes_of_administration = Oral, rectal
<!--Pharmacokinetic data-->
| bioavailability = 2.4–36% (oral)
| protein_bound = 55%
| metabolism = Hepatic ([[CYP1A2]])
| elimination_half-life = 2–4 hours
| excretion = Renal
<!--Identifiers-->
| IUPHAR_ligand = 6687
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 321-64-2
| ATC_prefix = N06
| ATC_suffix = DA01
| ATC_supplemental = 
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00382
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 1859
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4VX7YNB537
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 45980
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 95
| PDB_ligand = THA
<!--Chemical data-->
| C=13 | H=14 | N=2
| melting_point = 183
| boiling_point = 358
| smiles = n1c3c(c(c2c1cccc2)N)CCCC3
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| 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_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = YLJREFDVOIBQDA-UHFFFAOYSA-N
}}

'''Tacrine''' is a centrally acting [[anticholinesterase inhibitor|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.<ref>{{cite journal | vauthors = Taraschenko OD, Barnes WG, Herrick-Davis K, Yokoyama Y, Boyd DL, Hough LB | title = Actions of tacrine and galanthamine on histamine-N-methyltransferase | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 27 | issue = 3 | pages = 161–165 | date = April 2005 | pmid = 15834447 | doi = 10.1358/mf.2005.27.3.890872 }}</ref>

==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.<ref>{{cite patent | country = US | number = 4816456 | inventor = Summers WK | gdate = 28 March 1989| title = Administration of monoamine acridines in cholinergic neuronal deficit states}}</ref><ref>{{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 }}</ref><ref>{{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 }}</ref>  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.<ref name="Qizilbash1998">{{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 }}</ref><ref name="Rang2003">{{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}}.</ref>

Tacrine has been discontinued in the [[United States of America|US]]<ref name=MSR>{{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}}</ref> in 2013, due to concerns over safety.<ref>{{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 }}</ref>

Tacrine was also described as an [[analeptic]] agent used to promote mental alertness.<ref name="ElksGanellin1990">{{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}}</ref>

==Adverse effects==
;Very common (>10% incidence) adverse effects include<ref name = MSR />
{{div col|colwidth=20em}}
* Increased [[liver function tests]] (LFT), with 49% of patients displaying elevated [[Alanine transaminase|ALA]]<ref>{{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 }}</ref>
* Diarrhea
* Dizziness
* Headache
* Nausea
* Vomiting
{{Div col end}}

;Common (1-10% incidence) adverse effects include<ref name = MSR /><ref name = DD />
{{div col|colwidth=20em}}
* 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
{{Div col end}}

;Uncommon/rare (<1% incidence) adverse effects include<ref name = DD />
{{div col|colwidth=20em}}
* [[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
{{Div col end}}

;Unknown incidence adverse effects include<ref name = DD />
{{div col|colwidth=20em}}
* [[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)
{{Div col end}}

=== 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.<ref name = DD />

==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.<ref name = DD>Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.</ref>

== References ==
{{reflist}}

== External links ==
*[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]]