Tacrine

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. 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.

Adverse effects

;Very common (10% incidence) adverse effects include

• Increased liver function tests (LFT), with 49% of patients displaying elevated ALA
• Diarrhea
• Dizziness
• Headache
• Nausea
• Vomiting

;Common (1-10% incidence) adverse effects include

• Abdominal pain
• Agitation
• Anxiety
• Ataxia — decreased control over bodily movements.
• Belching
• Confusion
• Conjunctivitis (a link to tacrine treatment has not been conclusively proven)
• Constipation
• Diaphoresis — sweating.
• Fatigue
• Hallucinations
• Indigestion
• Insomnia
• Myalgia — muscle pain
• Rash
• Rhinitis
• Somnolence
• Tremor
• Urinary incontinence
• Weight loss

;Uncommon/rare (

• 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.
• Hepatotoxicity (that is toxic effects on the liver)
• Ototoxicity (hearing/ear damage; a link to tacrine treatment has not been conclusively proven)
• Seizures
• Taste changes

;Unknown incidence adverse effects include

• Bradycardia
• Delirium
• Depression
• Hypotension
• Suicidal ideation and behaviour
• Urinary tract infection
• Other optic effects such as glaucoma, cataracts, etc. (also not conclusively linked to tacrine treatment)

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.

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.

References

References

1. Anvisa. (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial". [[Diário Oficial da União]].
2. (April 2005). "Actions of tacrine and galanthamine on histamine-N-methyltransferase". Methods and Findings in Experimental and Clinical Pharmacology.
3. "Administration of monoamine acridines in cholinergic neuronal deficit states".
4. (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.
5. (25 March 2005). "New Mexico Doctor invents drugs, supplements for Alzheimer's disease, Multiple Sclerosis.". NM Bus Weekly.
6. (November 1998). "Cholinesterase inhibition for Alzheimer disease: a meta-analysis of the tacrine trials. Dementia Trialists' Collaboration". JAMA.
7. (2003). "Pharmacology". Churchill Livingstone.
8. "tacrine (Discontinued) - Cognex". WebMD.
9. "Tacrine". U.S. National Institutes of Health.
10. (1990). "Dictionary of Drugs".
11. (April 1994). "Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease". JAMA.
12. Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 8]. Greenwood Village, CO: Thomsen Healthcare; 2013.