Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer's disease

To explore further the potential for cognitive enhancement utilizing nicoti nic stimulation in Alzheimer's disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of th e novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures desi gn. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvem ents were seen in non-verbal learning tasks such as spatial learning and me mory, and repeated acquisition. No significant behavioral, vital sign, or p hysical side effects were seen. These results confirm that stimulating cent ral nicotinic receptors has acute cognitive benefit in AD patients. These f indings suggest that selective ChCAs have a potential therapeutic role in d ementing disorders, and that further studies with this or similar agents in AD and/or Parkinson's disease are warranted.