A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)- 2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions.
The title compound (T-588) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T-588 at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T-588 exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.
Ono
S
S
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Yamafuji
T
T
Chaki
H
H
Todo
Y
Y
Maekawa
M
M
Kitamura
K
K
Kimura
T
T
Nakada
Y
Y
Mozumi
K
K
Narita
H
H
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D004048:Diethylamines / Q000627:therapeutic use* / Q000633:toxicity; D000860:Hypoxia / Q000188:drug therapy*; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D018377:Neurotransmitter Agents / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use*; D016548:Prosencephalon / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013876:Thiophenes / Q000627:therapeutic use* / Q000633:toxicity
D004048:Diethylamines; D018377:Neurotransmitter Agents; D018697:Nootropic Agents; D013876:Thiophenes; C082372:T 588