Very little can be done to abate or control the progression of dementia, a clinical syndrome most commonly encountered later in life and manifested by impairments in cognition, language, and memory. The percentage of the world's elderly population is increasing, and so too is the need for effective pharmaceutical interventions for dementias such as Alzheimer's disease (AD), age‐associated memory impairment (AAMI), multi‐infarct dementia (MID), vascular dementia, and Parkinsonian dementia. Advances have been made in understanding the etiology of these diseases, but much remains to be discovered. In this chapter we have focused on the development of several therapeutic approaches that have in common the ability to modulate gated ion channels, and as such, have the potential to affect multiple neurotransmitter systems. Specifically, we discuss the structure‐activity relationship (SAR) and behavioral outcome for ligands interacting with the (1) γ‐aminobutyric acid subtype A benzodiazepine receptor (GABA A /BzR); (2) nicotinic acetylcholine receptor (nAChR); (3) serotonin subtype 3 receptor (5‐HT 3 R); and (4) the potassium M‐channel.

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Relatively few effective therapies exist for the multitude of disorders that comprise dementia, a clinical syndrome manifested by impairments in cognition. language and memory. Treatment of Alzheimer's disease (AD), the most common cause or dementia, is a primary goal of research in cognitive enhancement. However, despite intense research, effective pharmacological interventions remain to be developed. The preponderance of pharmacological strategies which are being pursued in AD research attempt to relieve cognitive and memory deficits which are attributed to cholinergic dysfunction. This paper briefly reviews the status of other efforts that have in common the potential to enhance the use-dependent activity of multiple neurotransmitters system through the modulation of gated ion channels. Discussed are recent advances in the areas of: 1) y-aminobutyric acid subtype A receptor/benzodiazepine (GABAA/BZ) inverse agonists; 2) nicotinic acetylcholine receptor (nAChR) agonists; 3) serotonin subtype 3 receptor (5-HT3R) antagonists; and 4) potassium (K+) M-channel inhibitors.