Tacrine for Treating Alzheimer's Disease

Tacrine (tetrahydroaminoacridine, THA) was first available in Australia in the mid 1940s when it was used with morphine to lessen respiratory depression without affecting analgesia.¹Its anticholinesterase activity eventually led to clinical trials in patients with presumptive Alzheimer's disease (AD), but these pilot studies demonstrated only modest efficacy using tacrine alone²or in combination with lecithin.³Consistent findings of a cholinergic deficit in AD make such cholinergic manipulation a theoretically attractive palliative treatment. Trials of other cholinomimetics, however, had shown at best modest results and often practical limitations—eg, choline causes a fishy skin odor and the 30-minute half-life of physostigmine is too brief for lasting clinical effects. See also p 2523. Scientific and public interest, as well as controversy, exploded in 1986 when Summers and colleagues⁴reported dramatic results from a double-blind, placebo-controlled trial of tacrine in 17 patients with apparent clinical diagnoses of AD. One