Abstract
The chapter presents a systematic and fairly logical narrative of studies that have been performed over the past few years to understand the medicinal chemistry and neuronal nicotinic cholinergic (nACh) receptor binding of nicotinic ligands. The medicinal chemistry of nicotinic cholinergic ligands suffers from several major problems that are related to multiple subtypes of receptors (making it difficult to determine selectivity), species differences, and efficacy issues. New nicotinic ligands have proliferated at an unprecedented rate over the past decade, but few can be claimed to be truly selective. The binding of relatively few agents has been examined at multiple nACh populations, and even less is known concerning their functional (agonist, partial agonist, and antagonist) activity at each subtype. As a consequence, it is nearly impossible to refer to any of the ligands as being a selective agonist or selective antagonist. A further complication arises from agents that interact with nACh receptors in a non-competitive fashion that might have an indirect influence on binding or functional activity.
Published Version
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