doi:10.1038/nindia.2009.263 Published online 31 July 2009
A new class of organic compounds could disrupt the formation of harmful plaques in Alzheimer's disease (AD)1. The compounds could also enhance learning and memory by binding to a specific receptor molecule in brain regions such as cerebral cortex and hippocampus.
The findings of this research may yield potential drug candidates to treat AD related dementia.
Studies have shown that the M1 acetylcholine muscarinic receptor (mAChR) expressed in the cerebral cortex and hippocampus plays a major role in cognitive processing including short-term memory. Targeting this receptor, the researchers synthesized eight N-aryl carboxamide substituted 3-morpholino arecoline derivatives (9a-9h). Arecoline, an alkaloid obtained from the betel nut (Areca catechu), is the fruit of a palm tree.
Arecoline derivatives were tested on cultured brain cells to restore memory and learning in male rats. Two arecoline derivatives (9b and 9c) showed better performance in reversing scopolamine-induced dementia.
"Of all the derivatives, one derivative (9b) proved most effective and could emerge as the potent molecule having anti-dementia activity," says lead researcher S. Rangappa Kanchugarakoppal.
The authors of this work are from: Department of Studies in Chemistry, University of Mysore and Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
- Malviya, M. et al. Muscarinic receptor 1 agonist activity of novel N-aryl carboxamide substituted 3-morpholino arecoline derivatives in Alzheimer's presenile dementia models. Bioorg. Med. Chem. 17, 5526-5534 (2009) | Article |