Central nicotinic receptor agonists ABT-418, ABT-089, and (-)-nicotine reduce distractibility in adult monkeys

Mark A. Prendergast, William J. Jackson, Alvin V. Terry, Michael W. Decker, Stephen P. Arneric, Jerry J. Buccafusco

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


Increased distractibility is associated with both Alzheimer's disease and attention deficit disorder. The present study examined the effects of (-)-nicotine and the novel central nicotinic receptor (nAChR) agonists ABT-418 [(S)-3-methyl-2-pyrrolidinyl)isoxazole] and ABT-089 [2-metoyl-3-(2-(S)-pyrrolindinylmethoxy)-pyridine dihydrochloride] on the delayed recall accuracy of adult monkeys exposed to distracting stimuli. Unpredictable exposure to a random visual array produced marked decrements in recall accuracy on trials with the shortest delay intervals, reducing the accuracy on these trials by 23.4%. Intramuscular (IM) administration of (-)-nicotine, in doses of 5.4-43.3 nmol/kg, attenuated the effect of the distractor, but did not completely prevent it. Both ABT-418 (2.0-16.2 nmol/kg, IM) and ABT-089 (16.4-32.8 nmol/kg, IM) prevented distractibility, producing increases of 7.5-25.0% in accuracy on trials disrupted by distractor exposure. Further, both compounds also improved accuracy on trials during which distractors were not presented, an effect which was not observed after (-)-nicotine administration. Nicotinic-mediated side effects were not observed following administration of any compound. Thus, nAChR stimulation reduces distractibility in adult monkeys and may, therefore, represent a target for the pharmacologic treatment of disorders associated with susceptibility to distraction. ABT-418 and ABT-089 appear to be particularly useful in this regard, a likely result of their selective agonist activity at nAChRs expressed in the brain.

Original languageEnglish
Pages (from-to)50-58
Number of pages9
Issue number1
StatePublished - 1998

Bibliographical note

Funding Information:
&p.2: wledgements The authors wish to thank Nancy Kille for her technical assistance in the completion of this project. In addition, Patricia Ryan is thanked for her administrative assistance. This work was supported by a grant from the Pharmaceuticals Products Division of Abbott Laboratories and the Office of Research and Development, Medical Research Service, Department of Veterans Affairs. Preliminary data were presented at the 2nd Annual Duke Nicotine Symposium, November 1996, Duke University Medical Center, Durham, NC.


  • (-)-Nicotine
  • ABT-089
  • ABT-418
  • Cognition
  • Delay matching
  • Distractibility
  • Monkey

ASJC Scopus subject areas

  • Pharmacology


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