Tacrine is a centrally acting anticholinesterase and indirect cholinergic

Cholinergic

The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 agonist (parasympathomimetic). It was the first centrally-acting cholinesterase inhibitor approved for the treatment of Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

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

Adrien Albert

Adrien Albert was a leading authority in the development of medicinal chemistry in Australia. Albert also authored many important books on chemistry, including one on selective toxicity....

 at the University of Sydney

University of Sydney

The University of Sydney is a public university located in Sydney, New South Wales. The main campus spreads across the suburbs of Camperdown and Darlington on the southwestern outskirts of the Sydney CBD. Founded in 1850, it is the oldest university in Australia and Oceania...

. It also acts as a histamine N-methyltransferase

Histamine N-methyltransferase

Histamine N-methyltransferase is one of two enzymes involved in the metabolism of histamine. The other being diamine oxidase. Histamine N-methyltransferase catalyzes the methylation of histamine in the presence of S-adenosylmethionine forming N-methylhistamine. HMT is present in most body tissues...

 inhibitor.

Clinical use

Tacrine was the prototypical cholinesterase inhibitor for the treatment of Alzheimer's disease

Alzheimer's disease

Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

. 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.

The use of tacrine is limited by poor oral bioavailability

Bioavailability

In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

, the necessity for four-times daily dosing, and considerable adverse drug reaction

Adverse drug reaction

An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...

s (including nausea

Nausea

Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, diarrhea

Diarrhea

Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, urinary incontinence

Urinary incontinence

Urinary incontinence is any involuntary leakage of urine. It is a common and distressing problem, which may have a profound impact on quality of life. Urinary incontinence almost always results from an underlying treatable medical condition but is under-reported to medical practitioners...

 and hepatotoxicity

Hepatotoxicity

Hepatotoxicity implies chemical-driven liver damage.The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses and sometimes even when introduced within therapeutic ranges, may injure...

) such that few patients could tolerate therapeutic doses.

Newer cholinesterase inhibitors, such as donepezil

Donepezil

Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...

, are now preferred over tacrine.

Overdosage/Toxicity

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 anticholinergic

Anticholinergic

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....

s, such as atropine

Atropine

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

, 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.

See also

• Alzheimer's disease
  Alzheimer's disease
  Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
  
  
• Cholinesterase inhibitor