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

Psychopharmacology (Berl). 1998 Mar;136(1):50-8. doi: 10.1007/s002130050538.

Abstract

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-methyl-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 (i.m.) 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, i.m.) and ABT-089 (16.4-32.8 nmol/kg, i.m.) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Attention / drug effects*
  • Cholinergic Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Isoxazoles / pharmacology*
  • Macaca mulatta
  • Macaca nemestrina
  • Male
  • Mental Recall / drug effects
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Photic Stimulation
  • Pyridines / pharmacology*
  • Pyrrolidines / pharmacology*
  • Receptors, Nicotinic / drug effects*

Substances

  • Anti-Anxiety Agents
  • Cholinergic Agents
  • Isoxazoles
  • Nicotinic Agonists
  • Pyridines
  • Pyrrolidines
  • Receptors, Nicotinic
  • 3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole
  • Nicotine
  • pozanicline