title: The acute effects of dimebolin, a potential Alzheimer's disease treatment, on working memory in rhesus monkeys.
abstract: BACKGROUND
  Dimebolin (latrepirdine), a compound with multiple potential drug targets, is being evaluated in clinical trials for the treatment of Alzheimer's disease (AD) and preliminary results suggest it can slow the disease process. There is also evidence that dimebolin directly improves aspects of cognition. Here we examined the acute effect of dimebolin on components of working memory in non-human primates, young adult (11-17 years old) and aged (20-31 years old) rhesus macaques.
  
  
  METHODS
  The effects of dimebolin (3.9-118 µg kg(-1)) on working memory, as measured by performance on delayed matching-to-sample (DMTS), were examined in the normal young adult monkeys and aged adult monkeys. All the monkeys studied were proficient in the performance of a computer-assisted DMTS task. In a subsequent experiment in the same subjects, dimebolin was administered 15 min before a cognitively-impairing dose (20 µg kg(-1)) of scopolamine.
  
  
  RESULTS
  In both the young adult and aged monkeys, dimebolin significantly increased the DMTS task accuracies. In young adults, the task improvement was associated with long (retention/retrieval) delay trials, and a protracted enhancement was observed for sessions run 24 h post administration of a single dose. Dimebolin did not significantly attenuate the scopolamine-induced impairment. In the aged monkeys, dimebolin significantly improved the reduced task accuracies associated with long delay intervals.
  
  
  CONCLUSIONS
  Here we demonstrated that dimebolin is able to improve components of working memory in monkeys and to induce a protracted response for at least 24 h after administration of a single dose.
authors.affiliation: Department of Pharmacology and Toxicology, Alzheimer's Research Center, Medical College of Georgia, Augusta, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Webster
authors.forename: Christina A
authors.initials: CA
authors.lastname: Wilson
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Eric G
authors.initials: EG
authors.lastname: Mohler
authors.forename: Alvin V
authors.initials: AV
authors.lastname: Terry
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Buccafusco
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology
chemical_list: D007211:Indoles; D012601:Scopolamine; C010119:latrepirdine