Tacrine

drugbox
IUPAC_name = 1,2,3,4-tetrahydroacridin-9-amine

---

width = 132
CAS_number = 321-64-2
ATC_prefix = N06
ATC_suffix = AA18
ATC_supplemental = ATC|N06|DA01
PubChem = 1935
ChemSpiderID = 1859
DrugBank = APRD00690
C=13 | H=14 | N=2
molecular_weight = 198.264 g/mol
bioavailability = 2.4–36% (oral)
protein_bound = 55%
metabolism = Hepatic (CYP1A2)
elimination_half-life = 2–4 hours
excretion = Renal
pregnancy_category = C (Au), C (U.S.)
legal_status = S4 (Au), POM (UK), ℞-only (U.S.)
routes_of_administration = 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.

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.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.]

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.Sweetman S, editor. Martindale: the complete drug reference, 34th ed. London: Pharmaceutical Press; 2004. ISBN 0-85369-550-4]

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

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

ee also

*Alzheimer's disease
*Cholinesterase inhibitor