Clinical Aspects of Nicotinic Agents: Therapeutic Applications in Central Nervous System Disorders

Abstract

Advances in the understanding of the structure, function, and distribution of central nervous system (CNS) nicotinic receptors has provided the impetus for new studies examining the role(s) that these receptors and associated processes may play in CNS functions. Further motivation has come from the realization that such receptors must be involved in the maintenance of cigarette smoking and from clues from studies of degenerative neurologic diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) where the loss of nicotinic receptors has been described (NUPORDBERG 1994). Ongoing investigations of the molecular substructure of CNS nicotinic receptors and their pharmacology have begun to open up new possibilities for novel CNS therapeutics with nicotinic agents (AUPRNERIC et al. 1995). Exploiting these possibilities will require an understanding of the role(s) that these receptor systems play in human cognitive, behavioral, motor, and sensory functioning. Clues from careful studies of human cognition and behavior are beginning to emerge and will provide direction for studies of potentially therapeutic novel nicotinic agents. There is considerable evidence for the involvement of CNS nicotinic cholinergic receptors in a variety of cognitive, motor, and behavioral systems. Modulation of these receptors with the ultimate goal of producing therapeutic benefits is the goal of these investigations and of drug development.