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 nicotinic stimulation in Alzheimer's disease (AD), six otherwise healthy subjects with moderate AD received placebo and three doses (6, 12, and 23 mg) of the novel selective cholinergic channel activator (ChCA) (nicotinic agonist) ABT-418 over 6 h in a double-blind, within-subjects, repeated-measures design. Subjects showed significant improvements in total recall and a decline in recall failure on a verbal learning task. Qualitatively similar improvements were seen in non-verbal learning tasks such as spatial learning and memory, and repeated acquisition. No significant behavioral, vital sign, or physical side effects were seen. These results confirm that stimulating central nicotinic receptors has acute cognitive benefit in AD patients. These findings suggest that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson's disease are warranted.
Potter
A
A
Department of Psychiatry, University of Vermont College of Medicine, Burlington 05401, USA.
Corwin
J
J
Lang
J
J
Piasecki
M
M
Lenox
R
R
Newhouse
P A
PA
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007555:Isoxazoles / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D011597:Psychomotor Performance / Q000187:drug effects; D011759:Pyrrolidines / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D007555:Isoxazoles; D018722:Nicotinic Agonists; D011759:Pyrrolidines; C088383:3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole; D011388:Prolactin; D006854:Hydrocortisone