Category: pharmacological
Aliases: Cognex, tetrahydroaminoacridine, THA
Reversible acetylcholinesterase inhibitor — first medication approved (1993) for Alzheimer disease. Withdrawn from US market in 2013 because of hepatotoxicity (asymptomatic ALT elevations in 30-50% of patients, with frank hepatitis in a minority). Almost entirely metabolized by CYP1A2, making it the textbook CYP1A2 victim in pharmacology education. Retained in the registry for reference data on CYP1A2 inhibitor potency despite the compound being clinically obsolete. PK (Cognex label, withdrawn 2013 for hepatotoxicity but PK well-characterized): Absolute F 17 ± 13% (low — extensive first-pass via CYP1A2), Tmax 1–2 h, t½ ~3 h (qid dosing). Apparent V 349 ± 193 L (large lipophilic distribution). Protein binding ~55%. Food reduces F by 30–40% (give ≥1 h before meals). The first FDA-approved AChE inhibitor for Alzheimer's, displaced by donepezil/rivastigmine/galantamine — kept in the registry for CYP1A2 victim modeling (fluvoxamine → tacrine 8.30× authored Wave 2a v1.1).
PO: 3h