Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. William K. Summers received a patent for this use in 1989.[3][4][5] 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.[6][7]
Tacrine has been discontinued in the US[8] in 2013, due to concerns over safety.[9]
Tacrine was also described as an analeptic agent used to promote mental alertness.[10]
Adverse Effects
Very common (>10% incidence) adverse effects include[8]
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.
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.[11]
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.[11]
^Taraschenko OD, Barnes WG, Herrick-Davis K, Yokoyama Y, Boyd DL, Hough LB (April 2005). "Actions of tacrine and galanthamine on histamine-N-methyltransferase". Methods and Findings in Experimental and Clinical Pharmacology. 27 (3): 161–165. doi:10.1358/mf.2005.27.3.890872. PMID15834447.
^US 4816456, Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", issued 28 March 1989
^Waldholz M (4 August 1987). 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 (Report). p. A-1.
^Qizilbash N, Whitehead A, Higgins J, Wilcock G, Schneider L, Farlow M (November 1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA. 280 (20): 1777–1782. doi:10.1001/jama.280.20.1777. PMID9842955.
^Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN978-0-443-07145-4..