Tacrine

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Tacrine
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Identifiers
CAS number	321-64-2
ATC code	N06AA18 N06 DA01
PubChem	1935
DrugBank	APRD00690
Chemical data
Formula	C₁₃H₁₄N₂
Mol. mass	198.264 g/mol
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Half life	2–4 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	C (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral, rectal

Tacrine is a parasympathomimetic and a centrally acting cholinesterase inhibitor (anticholinesterase). 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.

[edit] Clinical use

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. Studies have found that it may have a small beneficial effect on cognition and other clinical measures, though adequate study data is limited and the clinical relevance of these findings is unclear.^[1]^[2]

The use of tacrine is limited by poor oral bioavailability, the necessity for four-times daily dosing, and considerable adverse drug reactions (including nausea, diarrhea, urinary incontinence and hepatotoxicity) such that few patients could tolerate therapeutic doses.^[3]

Other newer cholinesterase inhibitors, such as donepezil, are now preferred over tacrine.

[edit] References

^ Qizilbash N, Whitehead A, Higgins J, et al. Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. JAMA 1998;280(20):1777-82. PMID 9842955
^ Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology, 5th edition. Edinburgh: Churchill Livingstone; 2003.
^ Sweetman S, editor. Martindale: the complete drug reference, 34th ed. London: Pharmaceutical Press; 2004. ISBN 0-85369-550-4