Effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946), a novel cognition activator, on learning and memory in rodent models.
We examined the effects of N-[2-(1-azabicyclo[3,3,0]octan-5-yl)ethyl]2-nitroaniline fumarate (SK-946) on cognition in various rodent models. SK-946 slightly suppressed spontaneous motor activity, but had no effect on scopolamine-induced motor facilitation. SK-946 ameliorated scopolamine-, pirenzepine-, cycloheximide- and electric shock-induced passive avoidance deficits in rodents when administered before acquiring the training. In an active avoidance test, SK-946 accelerated avoidance acquisition in the later half of training without a marked increase in lever-pressing. In more reliable models of cognitive disorders, i.e. an AF64A intracerebroventricular infusion model using the step-through passive avoidance test, an aged rat model using the step-down passive avoidance test and methylazoxymethanol (MAM)-induced microencephalic rat model using the Morris water maze test, SK-946 ameliorated impaired learning and memory. These results suggest an ability of SK-946 to enhance cognitive functions.
Pharmaceutical Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
T
T
Suzuki
K
K
Hirooka
K
K
Kanda
H
H
Hirooka
K
K
Furusawa
D000375:Aging / Q000502:physiology; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning; D001388:Aziridines / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D007858:Learning / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects
D000814:Aniline Compounds; D001388:Aziridines; D001643:Bridged Bicyclo Compounds; D018721:Muscarinic Agonists; C107666:N-(2-(1-azabicyclo(3.3.0)octan-5-yl)ethyl)-2-nitroaniline; D009466:Neuromuscular Blocking Agents; D018697:Nootropic Agents; D011976:Receptors, Muscarinic; C044894:ethylcholine aziridinium; D002794:Choline