Tacrine
Clinical data | |
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Trade names | Cognex |
AHFS/Drugs.com | Monograph |
MedlinePlus | a693039 |
Pregnancy category |
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Routes of administration | Oral, rectal |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 2.4–36% (oral) |
Protein binding | 55% |
Metabolism | Hepatic (CYP1A2) |
Elimination half-life | 2–4 hours |
Excretion | Renal |
Identifiers | |
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JSmol) | |
Melting point | 183 °C (361 °F) |
Boiling point | 358 °C (676 °F) |
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Tacrine is a centrally acting
Clinical use
Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease. William K. Summers received a patent for this use in 1989.[3][4][5] 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.[6][7]
Tacrine has been discontinued in the
Tacrine was also described as an analeptic agent used to promote mental alertness.[10]
Adverse Effects
- Very common (>10% incidence) adverse effects include[8]
- Increased liver function tests (LFT)
- Nausea
- Vomiting
- Diarrhea
- Headache
- Dizziness
- 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
- Hallucinations
- Agitation
- Conjunctivitis (a link to tacrine treatment has not been conclusively proven)
- Diaphoresis — sweating.
- Uncommon/rare (<1% incidence) adverse effects include[11]
- 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[11]
- Urinary tract infection
- Delirium
- Other optic effects such as 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.[11]
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.[11]
References
- ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- PMID 15834447.
- ^ US 4816456, Summers WK, "Administration of monoamine acridines in cholinergic neuronal deficit states", issued 28 March 1989
- ^ Waldholz M (4 August 1987). 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-for research Furor. Wall Street Journal (Report). p. A-1.
- ^ Peacock D (25 March 2005). "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis". NM Bus Weekly.
- PMID 9842955.
- ISBN 978-0-443-07145-4..
- ^ a b c "tacrine (Discontinued) - Cognex". Medscape Reference. WebMD. Archived from the original on 30 June 2019. Retrieved 8 October 2013.
- ^ "Tacrine". LiverTox. U.S. National Institutes of Health. Archived from the original on 2019-07-02.
- ISBN 978-1-4757-2087-7.
- ^ a b c d e Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.
External links
- Acetylcholinesterase: A gorge-ous enzyme QUite Interesting PDB Structure article at PDBe