Cognition enhancement strategies by ion channel modulation of neurotransmission

Relatively few effective therapies exist for the multitude of disorders tha t comprise dementia, a clinical syndrome manifested by impairments in cogni tion, language and memory. Treatment of Alzheimer's disease (AD), the most common cause of dementia, is a primary goal of research in cognitive enhanc ement. However, despite intense research, effective pharmacological interve ntions remain to be developed. The preponderance of pharmacological strateg ies which are being pursued in AD research attempt to relieve cognitive and memory deficits which are attributed to cholinergic dysfunction. This pape r briefly reviews the status of other efforts that have in common the poten tial to enhance the use-dependent activity of multiple neurotransmitters sy stem through the modulation of gated ion channels. Discussed are recent adv ances in the areas of: 1) gamma-aminobutyric acid subtype A receptor/benzod iazepine (GABA(A)/BZ) inverse agonists; 2) nicotinic acetylcholine receptor (nAChR) agonists; 3) serotonin subtype 3 receptor (5-HT3R) antagonists; an d 4) potassium (K+) M-channel inhibitors.