Tacrine

Tacrine
Clinical data
Trade names	Cognex
AHFS/Drugs.com	Monograph
MedlinePlus	a693039
Pregnancy; category	AU: C; US: C (Risk not ruled out); ;
Routes of; administration	Oral, rectal
ATC code	N06DA01 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only) ; BR: Class C1 (Other controlled substances) ; UK: POM (Prescription only) ; US: ℞-only ;
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Elimination half-life	2–4 hours
Excretion	Renal
Identifiers
	IUPAC name 1,2,3,4-Tetrahydroacridin-9-amine;
CAS Number	321-64-2 ;
IUPHAR/BPS	6687;
DrugBank	DB00382 ;
ChemSpider	1859 ;
UNII	4VX7YNB537;
ChEBI	CHEBI:45980 ;
ChEMBL	ChEMBL95 ;
PDB ligand	THA (PDBe, RCSB PDB);
Chemical and physical data
Formula	C13H14N2
Molar mass	198.269 g·mol−1
3D model (JSmol)	Interactive image;
Melting point	183 °C (361 °F)
Boiling point	358 °C (676 °F)
	SMILES n1c3c(c(c2c1cccc2)N)CCCC3;
	InChI 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) ; Key:YLJREFDVOIBQDA-UHFFFAOYSA-N ;
	(verify)

Short description: Chemical compound

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.^[1]

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.^[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 United States of America ^[7] in 2013, due to concerns over safety.^[8]

Tacrine was also described as an analeptic agent used to promote mental alertness.^[9]

Adverse Effects

Very common (>10% incidence) adverse effects include^[7]

Increased liver function tests (LFT)
Nausea
Vomiting
Diarrhea
Headache
Dizziness

Common (1-10% incidence) adverse effects include^[7]^[10]

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^[10]

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^[10]

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

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.^[10]

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.^[10]

References

↑ "Actions of tacrine and galanthamine on histamine-N-methyltransferase". Methods and Findings in Experimental and Clinical Pharmacology 27 (3): 161–165. April 2005. doi:10.1358/mf.2005.27.3.890872. PMID 15834447.
↑ Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", US patent 4816456, issued 28 March 1989
↑ "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: A-1. 4 August 1987.
↑ "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis.". NM Bus Weekly. 25 March 2005. https://www.bizjournals.com/albuquerque/stories/2005/03/28/smallb2.html.
↑ "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA 280 (20): 1777–1782. November 1998. doi:10.1001/jama.280.20.1777. PMID 9842955.
↑ Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. 2003. ISBN 978-0-443-07145-4. .
↑ ^7.0 ^7.1 ^7.2 "tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. http://reference.medscape.com/drug/tacrine-343070.
↑ "Tacrine". LiverTox. U.S. National Institutes of Health. http://www.livertox.nih.gov/Tacrine.htm.
↑ Dictionary of Drugs. 1990. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7.
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.

External links

Acetylcholinesterase: A gorge-ous enzyme QUite Interesting PDB Structure article at PDBe

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Tacrine. Read more

[1] "Actions of tacrine and galanthamine on histamine-N-methyltransferase". Methods and Findings in Experimental and Clinical Pharmacology 27 (3): 161–165. April 2005. doi:10.1358/mf.2005.27.3.890872. PMID 15834447.

[2] Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", US patent 4816456, issued 28 March 1989

[3] "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: A-1. 4 August 1987.

[4] "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis.". NM Bus Weekly. 25 March 2005. https://www.bizjournals.com/albuquerque/stories/2005/03/28/smallb2.html.

[Qizilbash1998-5] "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA 280 (20): 1777–1782. November 1998. doi:10.1001/jama.280.20.1777. PMID 9842955.

[Rang2003-6] Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. 2003. ISBN 978-0-443-07145-4. .

[MSR-7] 7.0 ^7.1 ^7.2 "tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. http://reference.medscape.com/drug/tacrine-343070.

[8] "Tacrine". LiverTox. U.S. National Institutes of Health. http://www.livertox.nih.gov/Tacrine.htm.

[ElksGanellin1990-9] Dictionary of Drugs. 1990. doi:10.1007/978-1-4757-2085-3. ISBN 978-1-4757-2087-7.

[DD-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

v t e Psychoanaleptics: Anti-dementia agents (ATC code N06D and others)
AChE inhibitor medications	Donepezil Galantamine Ipidacrine Rivastigmine Tacrine
Other medications	Bifemelane Ginkgo folium Meclofenoxate (centrophenoxine) Memantine Nicergoline
Experimental BACE inhibitors	Lanabecestat Verubecestat