Tacrine

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Tacrine
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade namesCognex
AHFS/Drugs.commonograph
MedlinePlusa693039
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral, rectal
Pharmacokinetic data
Bioavailability2.4–36% (oral)
Protein binding55%
MetabolismHepatic (CYP1A2)
Half-life2–4 hours
ExcretionRenal
Identifiers
CAS number321-64-2 YesY
ATC codeN06DA01
DrugBankDB00382
ChemSpider1859 YesY
UNII4VX7YNB537 YesY
ChEBICHEBI:45980 YesY
ChEMBLCHEMBL95 YesY
Chemical data
FormulaC13H14N2 
Mol. mass198.264 g/mol
Physical data
Melt. point183 °C (361 °F)
Boiling point358 °C (676 °F)
 YesY (what is this?)  (verify)
 
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Tacrine
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade namesCognex
AHFS/Drugs.commonograph
MedlinePlusa693039
Pregnancy cat.C (AU) C (US)
Legal statusPrescription Only (S4) (AU) POM (UK) -only (US)
RoutesOral, rectal
Pharmacokinetic data
Bioavailability2.4–36% (oral)
Protein binding55%
MetabolismHepatic (CYP1A2)
Half-life2–4 hours
ExcretionRenal
Identifiers
CAS number321-64-2 YesY
ATC codeN06DA01
DrugBankDB00382
ChemSpider1859 YesY
UNII4VX7YNB537 YesY
ChEBICHEBI:45980 YesY
ChEMBLCHEMBL95 YesY
Chemical data
FormulaC13H14N2 
Mol. mass198.264 g/mol
Physical data
Melt. point183 °C (361 °F)
Boiling point358 °C (676 °F)
 YesY (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. See William_K._Summers He is listed as inventor of Tacrine. It also acts as a histamine N-methyltransferase inhibitor.

Clinical use[edit source | edit]

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.[1][2]

Newer cholinesterase inhibitors, such as donepezil, are now preferred over tacrine.[citation needed]

Overdosage/toxicity[edit source | edit]

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]

References[edit source | edit]

  1. ^ Qizilbash N, Whitehead A, Higgins J, et al. (1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials". Journal of the American Medical Association 280 (20): 1777–82. PMID 9842955. 
  2. ^ Rang HP, Dale MM, Ritter JM, Moore PK (2003). Pharmacology (5th ed. ed.). Edinburgh: Churchill Livingstone. ISBN 978-0-443-07145-4. .

External links[edit source | edit]

See also[edit source | edit]