STRUCTURE-ACTIVITY-RELATIONSHIPS OF NICOTINIC ACETYLCHOLINE-RECEPTOR AGONISTS AS POTENTIAL TREATMENTS FOR DEMENTIA

The ability of nicotine to enhance cognition in animals and humans and to exert neuroprotective and anxiolytic-like effects, as well as the negative correlation between smoking and Alzheimer's (and Parkinson's) disease, suggest a possible role for nicotinic agents in the treatment of some of the deficits that result from these conditions. Numerous compounds are known which activate neuronal nicotinic acety]choline receptors (nAChRs) and which might serve as lead compounds toward the development of such agents. The diversity of nAChRs suggests the possibility of developing selective compounds which would have more favorable side-effect profiles than the existing agents. An overview of the nicotinic system and model systems used to study nicotinic receptors is presented, followed by a discussion of structure-activity relationships of known lead compounds in assays that are thought to reflect therapeutic potential or possible side effects. (C) 1995 Wiley-Liss, Inc.