Tetrahydroaminoacridine (THA) as a pharmacological probe in Alzheimer's disease (AD) and other neurodegenerative disorders

Abstract Unlike other potent enhancers of cholinergic function in the central nervous system (CNS), THA appears to sustain improved function in many moderately impaired AD patients when the Summers procedure is followed. THA has a complex pharmacology. In addition to its enhancement of cholinergic transmission a hydroxylated metabolite might chelate aluminum (A1), thereby removing multiple toxicological constraints on CNS function. This mobilized THA metabolite-A1 complex might either be re-distributed to less sensitive sites or removed from the CNS across the blood-brain barrier (BBB). Since the known presence of A1 in AD brain is not necessarily causal, a positivistic approach to research and treatment with THA and its metabolites might serve to clarify this difficult and challenging problem.