title: High-affinity [3H]THA (tetrahydroaminoacridine) binding sites in rat brain.
abstract: 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.
authors.affiliation: Department of Neuroscience, Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
authors.forename: E E
authors.initials: EE
authors.lastname: Mena
authors.forename: M C
authors.initials: MC
authors.lastname: Desai
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D051381:Rats; D013619:Tacrine / Q000378:metabolism*
chemical_list: D013619:Tacrine; D000110:Acetylcholinesterase