Tacrine

Tacrine

Clinical data
Trade names	Cognex
AHFS/Drugs.com	Monograph
MedlinePlus	a693039
Pregnancy category	AU: C US: C (Risk not ruled out)
Routes of administration	Oral, rectal
ATC code	N06DA01 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	2.4–36% (oral)
Protein binding	55%
Metabolism	Hepatic (CYP1A2)
Biological half-life	2–4 hours
Excretion	Renal
Identifiers
IUPAC name 1,2,3,4-tetrahydroacridin-9-amine
CAS Number	321-64-2 Y
IUPHAR/BPS	6687
DrugBank	DB00382 Y
ChemSpider	1859 Y
UNII	4VX7YNB537 Y
ChEBI	CHEBI:45980 Y
ChEMBL	CHEMBL95 Y
PDB ligand ID	THA (PDBe, RCSB PDB)
ECHA InfoCard	100.005.721
Chemical and physical data
Formula	C13H14N2
Molar mass	198.264 g/mol
3D model (Jmol)	Interactive image
Melting point	183 °C (361 °F)
Boiling point	358 °C (676 °F)
SMILES n1c3c(c(c2c1cccc2)N)CCCC3
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

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.

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. William K. Summers received a patent for this use (US Patent No. 4,816,456). 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.

Tacrine has been discontinued in the US in 2013, due to concerns over safety.

Tacrine was also described as an analeptic agent used to promote mental alertness.

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.

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.