Tacrine is a centrally acting

acetylcholinesterase inhibitor Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level an ...

and indirect

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cation ...

agonist (

parasympathomimetic A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs becaus ...

). It was the first centrally acting cholinesterase inhibitor approved for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

, and was marketed under the trade name Cognex. Tacrine was first synthesised by Adrien Albert at the

University of Sydney The University of Sydney (USYD) is a public university, public research university in Sydney, Australia. Founded in 1850, it is the oldest university in both Australia and Oceania. One of Australia's six sandstone universities, it was one of the ...

in 1949. It also acts as a histamine N-methyltransferase inhibitor.

Clinical use

Tacrine was the prototypical

cholinesterase inhibitor Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine by cholinesterase. This increases the amount of the acetylcholine or butyryl ...

for the treatment of

. 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 An analeptic, in medicine, is a type of central nervous system (CNS) stimulant. The term ''analeptic'' typically refers to respiratory stimulants (e.g., doxapram). Analeptics include a wide variety of medications used to treat depression, attenti ...

agent used to promote mental alertness.

Adverse effects

;Very common (>10% incidence) adverse effects include * Increased

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...

(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 Conjunctivitis, also known as pink eye or Madras eye, is inflammation of the conjunctiva, the thin, clear layer that covers the white surface of the eye and the inner eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness ...

(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 (<1% incidence) adverse effects include *

Agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

(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 Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

* Delirium * Depression * Hypotension * Suicidal ideation and behaviour *

Urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

* Other optic effects such as

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or double vision, halos around ligh ...

, 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 Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

is a popular treatment for overdose.

Pharmacokinetics

Major form of metabolism is in the liver via hydroxylation of benzylic carbon by

CYP1A2 Cytochrome P450 1A2 (abbreviated CYP1A2), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the ''CYP1A2'' gene. Function ...

. This forms the major metabolite 1-hydroxy-tacrine (velnacrine) which is still active.Truven Health Analytics, Inc. DRUGDEX® System (Internet) ited 2013 Oct 8 Greenwood Village, CO: Thomsen Healthcare; 2013.

References

External links

Acetylcholinesterase: A gorge-ous enzyme
QUite Interesting PDB Structure article a
PDBe
{{Monoamine metabolism modulators Acetylcholinesterase inhibitors Antidementia agents