Tacrine

Tacrine

Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade names	Cognex
AHFS/Drugs.com	monograph
MedlinePlus	a693039
Pregnancy cat.	C (Au), C (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Routes	Oral, rectal
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Half-life	2–4 hours
Excretion	Renal
Identifiers
CAS number	321-64-2 Y
ATC code	N06AA18 N06DA01
PubChem	CID 1935
DrugBank	APRD00690
ChemSpider	1859 Y
UNII	4VX7YNB537 Y
ChEBI	CHEBI:45980 Y
ChEMBL	CHEMBL95 Y
Chemical data
Formula	C13H14N2
Mol. mass	198.264 g/mol
SMILES	eMolecules & PubChem
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) Y Key:YLJREFDVOIBQDA-UHFFFAOYSA-N Y
N (what is this?)  (verify)

Tacrine is a centrally acting anticholinesterase 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. It also acts as a histamine N-methyltransferase inhibitor.

Clinical use

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. 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.

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.

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 antidotes for overdose.

Major form of metabolism is in the liver via hydroxylation of benzylic carbon by Cytochrome P450 (CYP450). This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.^{[citation needed]}

See also

• Alzheimer's disease
• Cholinesterase inhibitor