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Tacrine
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Identifiers
CAS number 321-64-2
ATC code N06AA18 N06DA01
PubChem 1935
DrugBank APRD00690
ChemSpider 1859
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
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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. It also acts as a histamine N-methyltransferase inhibitor.

Contents

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]

Overdosage/Toxicity

As stated above, overdosage of tacrine may give rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Tertiary anticholinergics, such as atropine, may be used as an antidote for overdose.

Major form of metabolism is in the liver via hydroxylation of benzylic carbon by CYP450. This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.

References

  1. ^ 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
  2. ^ Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology, 5th edition. Edinburgh: Churchill Livingstone; 2003.
  3. ^ Sweetman S, editor. Martindale: the complete drug reference, 34th ed. London: Pharmaceutical Press; 2004. ISBN 0-85369-550-4

See also

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