High-affinity [3H]THA (tetrahydroaminoacridine) binding sites in rat brain.

Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor that is reported to have significant effects on cognition and memory in Alzheimer's disease patients, binds to rat brain membranes in a saturable and reversible manner. Computer analysis of the binding data revealed high- and low-affinity sites with Kd values of 97.8 nM and 4.65 microM and Bmax values of 4.13 and 114 pmol/mg protein. Autoradiographic studies show that these binding sites are not co-localized with acetylcholinesterase activity. The binding of [3H]THA to membranes does not appear to be related to receptors for several neurotransmitters/neuromodulators, including acetylcholine and other acetylcholinesterase inhibitors. Amiridin, a closely related acetylcholinesterase inhibitor, was able to block specific [3H]THA binding (IC50 = 1.05 microM). While the function of THA mediated by these sites is unknown, they may be responsible in part for the distinct clinical effects of tetrahydroaminoacridine compared to other acetylcholinesterase inhibitors.