Tacrine

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Tacrine
Tacrine2DACS.svg
Tacrine3Dan.gif
Systematic (IUPAC) name
1,2,3,4-tetrahydroacridin-9-amine
Clinical data
Trade names Cognex
AHFS/Drugs.com monograph
MedlinePlus a693039
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Routes of
administration		 Oral, rectal
Pharmacokinetic data
Bioavailability 2.4–36% (oral)
Protein binding 55%
Metabolism Hepatic (CYP1A2)
Biological half-life 2–4 hours
Excretion Renal
Identifiers
CAS Number 321-64-2 YesY
ATC code N06DA01 (WHO)
IUPHAR/BPS 6687
DrugBank DB00382 YesY
ChemSpider 1859 YesY
UNII 4VX7YNB537 YesY
ChEBI CHEBI:45980 YesY
ChEMBL CHEMBL95 YesY
PDB ligand ID THA (PDBe, RCSB PDB)
Chemical data
Formula C13H14N2
Molecular mass 198.264 g/mol
  • n1c3c(c(c2c1cccc2)N)CCCC3
  • 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) YesY
  • Key:YLJREFDVOIBQDA-UHFFFAOYSA-N YesY
Physical data
Melting point 183 °C (361 °F)
Boiling point 358 °C (676 °F)
  (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.[1]

Clinical use

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).[2][3][4] 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.[5][6]

Tacrine has been discontinued in the US[7] in 2013, due to concerns over safety.[8]

Adverse Effects

Very Common (>10% incidence) adverse effects include[7]
  • Increased LFTs
  • Nausea
  • Vomiting
  • Diarrhea
  • Headache
  • Dizziness
Common (1-10% incidence) adverse effects include[7][9]
  • Indigestion
  • Belching
  • Abdominal pain
  • Myalgia — muscle pain
  • Confusion
  • Ataxia — decreased control over bodily movements.
  • Insomnia
  • Rhinitis
  • Rash
  • Fatigue
  • Weight loss
  • Constipation
  • Somnolence
  • Tremor
  • Anxiety
  • Urinary incontinence
  • Hallucinatons
  • Agitation
  • Conjunctivitis (a link to tacrine treatment has not been conclusively proven)
  • Diaphoresis — sweating.
Uncommon/Rare (<1% incidence) adverse effects include[9]
  • 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.
  • Taste changes
Unknown incidence adverse effects include[9]
  • Urinary tract infection
  • Delirium
  • Other optic effects such as glaucoma, cataracts, etc. (also not conclusively linked to tacrine treatment)
  • Depression
  • Suicidal ideation and behaviour
  • Hypotension
  • Bradycardia

Overdose

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.[9]

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.[9]

References

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External links

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ {US Patent No. 4,816,456} http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=4,816,456.PN.&OS=PN/4,816,456&RS=PN/4,816,456
  3. ↑ Waldholz M. 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-forresearch Furor. Wall Street Journal. Tuesday August 4, 1987 p A-1
  4. ↑ Peacock D. New Mexico Doctor invents drugs, supplements for Alzheimer’s disease, Multiple Sclerosis. NM Bus Weekly. 25 MAR 2005
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found..
  7. ↑ 7.0 7.1 7.2 Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Tacrine at LiverTox
  9. ↑ 9.0 9.1 9.2 9.3 9.4 Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.
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