A novel anticholinesterase THB013: biochemical and behavioural studies.

Abstract

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.

• Authors: A Adem, A H Mohammed, B Winblad, B E Henriksson
• Journal: Journal of neural transmission. Parkinson's disease and dementia section (J Neural Transm Park Dis Dement Sect) Vol. 8 Issue 1-2 Pg. 139-48 ( 1994) ISSN: 0936-3076 [Print] Austria
• PMID: 7893376 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholinesterase Inhibitors
• Receptors, Muscarinic
• THB 013
• Tacrine
• Scopolamine

Topics

• Alzheimer Disease (drug therapy)
• Animals
• Behavior, Animal (drug effects)
• Cholinesterase Inhibitors (metabolism, pharmacology, therapeutic use)
• Male
• Maze Learning (drug effects)
• Models, Biological
• Rats
• Receptors, Muscarinic (drug effects)
• Scopolamine (pharmacology)
• Tacrine (analogs & derivatives, pharmacology, therapeutic use)