Competitive neuronal nicotinic receptor antagonists: a new direction for drug discovery

Neuronal nicotinic acetylcholine receptors are distributed extensively throughout the central and peripheral nervous systems. Currently, there is great interest in determining the structural and functional diversity of these receptors, and in developing subtype-selective agonists that have potential as therapeutic agents for neuropathology and disease. However, relatively little attention has been focused on the development of subtype-selective nicotinic receptor antagonists. Such antagonists would be beneficial for establishing the role of specific nicotinic receptor subtypes in physiological function and for unraveling the complexities of neuronal nicotinic receptor function. Furthermore, these subtype-selective antagonists may also prove to be beneficial in the treatment of neuropathology and disease. The current perspective summarizes the research that has been carried out with both classical competitive antagonists and more recently developed competitive nicotinic receptor antagonists.