Effect of a novel CNS-selective cholinesterase inhibitor, SM-10888, on habituation and passive avoidance responses in mice

Jpn J Pharmacol. 1990 Jun;53(2):211-20. doi: 10.1254/jjp.53.211.

Abstract

The effects of the tacrine (THA) derivative SM-10888 (9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine citrate) on habituation and passive avoidance responses were studied in mice. We examined its effects on habituation of exploratory activity, measured by photo-cell beam interruptions in a small, simple cage and cycloheximide (CXM)- or electroconvulsive shock (ECS)-induced stepdown type passive avoidance response (PAR) failures in comparison with those of THA, amiridin, HP-029 and physostigmine. SM-10888 (6 mg/kg, p.o.) administered post-acquisition session enhanced the retention of habituation. CXM- and ECS-induced PAR failures were improved by SM-10888 (6 mg/kg, p.o.) administered at pre-training or post-training, respectively. THA enhanced the retention of habituation and improved CXM-induced PAR failure at 30 mg/kg, p.o., but did not affect ECS-induced PAR failure at 1-15 mg/kg, p.o. Amiridin and HP-029 were also effective on habituation and CXM-induced PAR failure at 40-50 mg/kg, p.o., but did not affect ECS-induced PAR failure at the tested doses. Physostigmine showed a moderate improvement only in CXM-induced PAR failure. The results indicate that SM-10888 enhanced habituation and improved PAR failures at much lower doses than THA. This seems to depend on its high selectivity to the central nervous system.

MeSH terms

  • Aminacrine / analogs & derivatives
  • Aminacrine / pharmacology*
  • Aminoacridines / pharmacology*
  • Aminoquinolines / pharmacology
  • Animals
  • Avoidance Learning / drug effects*
  • Cholinesterase Inhibitors / pharmacology*
  • Cycloheximide / pharmacology
  • Electroshock
  • Exploratory Behavior / drug effects
  • Habituation, Psychophysiologic / drug effects*
  • Male
  • Mice
  • Physostigmine / pharmacology
  • Tacrine / analogs & derivatives
  • Tacrine / pharmacology

Substances

  • Aminoacridines
  • Aminoquinolines
  • Cholinesterase Inhibitors
  • 9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine
  • Tacrine
  • Aminacrine
  • Cycloheximide
  • Physostigmine
  • amiridine
  • velnacrine