title: Effects of NIK-247 on cholinesterase and scopolamine-induced amnesia.
abstract: The effects of NIK-247 on cholinesterase, scopolamine-induced amnesia and spontaneous movement were examined and compared with those of the well-known cholinesterase inhibitors tacrine and E-2020. NIK-247, tacrine and E-2020 all strongly inhibited acetylcholinesterase (AChE) in human red blood cells (IC50s = 1.0 x 10(-6), 2.9 x 10(-7) and 3.7 x 10(-8) M, respectively). In addition, NIK-247 and tacrine, but not E-2020, strongly inhibited butyrylcholinestrase (BuChE) in human serum. All three drugs produced mixed inhibition of AChE activity. Moreover, the inhibitory effect of NIK-247 on AChE was reversible. All compounds at 0.1-1 mg/kg p.o. significantly improved the amnesia induced by scopolamine (0.5 mg/kg s.c.) in rats performing a passive avoidance task. The three compounds at 1 and 3 mg/kg p.o. did not significantly decrease spontaneous movement by rats. These findings suggest that NIK-247 at a low dose (0.1-1 mg/kg p.o.) improves scopolamine-induced amnesia but does not affect spontaneous movement. The findings suggest that NIK-247 may be a useful drug for the treatment of Alzheimer's disease.
authors.affiliation: Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Ochiai
authors.forename: K
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects; D000544:Alzheimer Disease / Q000188:drug therapy; D000634:Aminoquinolines / Q000494:pharmacology*; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D002091:Butyrylcholinesterase / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000009:adverse effects*; D013619:Tacrine / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D011619:Psychotropic Drugs; D013619:Tacrine; D000077265:Donepezil; C049860:amiridine; D012601:Scopolamine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase