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Tacrine earns its spot in this archive on historical weight rather than obscurity; it was the first drug the FDA ever approved for Alzheimer's disease, launched in 1993 under the name Cognex and proof-of-concept that the cholinergic hypothesis (that boosting acetylcholine could meaningfully help Alzheimer's symptoms) actually worked in the clinic, opening the door for donepezil, rivastigmine, and galantamine to follow. That legacy came with a real cost; tacrine caused liver-enzyme elevations in roughly a quarter to half of treated patients, serious enough that trial protocols required stopping the drug if ALT rose above three times normal, and while the injury was almost always reversible on discontinuation, the burden of mandatory liver monitoring made tacrine impractical once safer, twice-a-day alternatives without the hepatotoxicity reached the market. Its manufacturer discontinued marketing tacrine in the United States in 2013, quietly retiring the drug that had started the entire cholinesterase-inhibitor era.
- first drug ever FDA-approved for Alzheimer's disease, establishing that cholinesterase inhibition produces real clinical benefit
- cognitive and functional improvement demonstrated in placebo-controlled Alzheimer's trials
- ALT elevations above 3x the upper limit of normal in roughly 25% or more of patients, usually appearing within 6-8 weeks of starting treatment
- required routine liver-enzyme blood monitoring throughout treatment
- GI side effects (nausea, vomiting) typical of acetylcholinesterase inhibitors
- Most patients who had to stop tacrine because of liver-enzyme elevations, about 88% in one large study, were able to successfully restart and continue the drug long-term once their ALT levels normalized.
Mechanism
Centrally acting, reversible inhibitor (a tetrahydroaminoacridine); raises levels by blocking its breakdown, with hepatotoxicity linked to its 7-hydroxy , a suspected precursor to a reactive quinone methide species.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Anyone who developed jaundice on tacrine could never be given it again; that was an absolute contraindication on the Cognex label, alongside fortnightly liver enzyme testing for everyone else. Beyond the liver it behaved like any cholinesterase inhibitor: nausea, vomiting, diarrhoea, a slowed heart rate, and aggravation of asthma, ulcer and urinary obstruction. Its interactions run through CYP1A2. Cimetidine raised tacrine exposure by about two thirds, smoking halved its half-life, tacrine roughly doubled theophylline levels, and it is synergistic with succinylcholine. Off the market since 2013, it still turns up in grey-market powders.
History
Originally synthesized decades earlier, then developed clinically through the 1980s and approved by the FDA in 1993 as Cognex, the first drug approved for Alzheimer's disease. Widespread transaminase elevations required routine liver monitoring, and it was gradually eclipsed by better-tolerated second-generation cholinesterase inhibitors, with US marketing discontinued in 2013.
Subjective profileweighing the evidence above
A historically pivotal first-of-its-kind drug whose liver-toxicity burden made it obsolete the moment safer alternatives arrived.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is tacrine still prescribed today?
No, its US manufacturer discontinued marketing it in 2013; newer cholinesterase inhibitors like donepezil offer similar benefit without tacrine's liver-monitoring burden and more convenient dosing.
Why is tacrine historically important if it's no longer used?
It was the first FDA-approved Alzheimer's drug, in 1993, and its approval validated the cholinergic hypothesis in humans, directly paving the way for donepezil, rivastigmine, and galantamine.
Adverse effects
- ALT elevations above 3x the upper limit of normal in roughly 25% or more of patients, usually appearing within 6-8 weeks of starting treatment
- required routine liver-enzyme blood monitoring throughout treatment
- GI side effects (nausea, vomiting) typical of acetylcholinesterase inhibitors