Effect of a novel CNS-selective cholinesterase inhibitor, SM-10888, on habituation and passive avoidance responses in mice.
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.
Okazaki
Y
Y
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Natori
K
K
Irie
T
T
Katsube
J
J
D000585:Aminacrine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000609:Aminoacridines / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004597:Electroshock; D005106:Exploratory Behavior / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D051379:Mice; D010830:Physostigmine / Q000494:pharmacology; D013619:Tacrine / Q000031:analogs & derivatives / Q000494:pharmacology
D000609:Aminoacridines; D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; C065164:9-amino-8-fluoro-1,2,3,4-tetrahydro-2,4-methanoacridine; D013619:Tacrine; D000585:Aminacrine; D003513:Cycloheximide; D010830:Physostigmine; C049860:amiridine; C056424:velnacrine