Tacrine

Tacrine

File:Tacrine2.png
File:Tacrine3d.png
Clinical data
Pregnancy category	C (Au), C (U.S.)
Routes of administration	Oral, rectal
ATC code	N06AA18 (WHO) N06DA01 (WHO)
Legal status
Legal status	S4 (Au), POM (UK), ℞-only (U.S.)
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Elimination half-life	2–4 hours
Excretion	Renal
Identifiers
IUPAC name 1,2,3,4-tetrahydroacridin-9-amine
CAS Number	321-64-2
PubChem CID	1935
DrugBank	APRD00690
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C13H14N2
Molar mass	198.264 g/mol

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.

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.

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

Overdosage/Toxicity

As stated above, overdosage of tacrine may giva rise to severe side effects such as nausea, vomiting, salivation, sweating, bradycardia, hypotension, collapse, and colvulsions. 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.

See also

• Alzheimer's disease
• Cholinesterase inhibitor