A novel anticholinesterase THB013: biochemical and behavioural studies.
Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. In this study, the biochemical effects of THA and one of these analogs, THB 013, on plasma cholinesterase activity, cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking the scopolamine induced disruption of spatial learning when administered 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.
Adem
A
A
Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Mohammed
A H
AH
Winblad
B
B
Henriksson
B E
BE
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008954:Models, Biological; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology; D013619:Tacrine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D002800:Cholinesterase Inhibitors; D011976:Receptors, Muscarinic; C092703:THB 013; D013619:Tacrine; D012601:Scopolamine