Interaction of tacrine and velnacrine with neocortical synaptosomal membranes: relevance to Alzheimer's disease.
The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes. Electron paramagnetic resonance employing a protein-specific spin label was used to monitor this interaction. Analogous to their effects in erythrocyte membranes [Butterfield and Rangachari (1992) Biochem. Biophys. Res. Commun. 185: 596-603], in the present studies both agents decreased segmental motion of spin labeled synaptosomal membrane proteins, consistent with increased cytoskeletal protein-protein interactions (0.001 < P < 0.005), and tacrine was more potent than velnacrine. These results are discussed with possible relevance to molecular actions of the agents and molecular alterations in Alzheimer's disease.
Butterfield
D A
DA
Department of Chemistry, University of Kentucky, Lexington 40506-0055.
Hensley
K
K
Hall
N
N
Umhauer
S
S
Carney
J
J
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000187:drug effects; D004578:Electron Spin Resonance Spectroscopy; D005849:Gerbillinae; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013570:Synaptic Membranes / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects; D013619:Tacrine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D003598:Cytoskeletal Proteins; D013619:Tacrine; C056424:velnacrine