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 we...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 1995/12/15, Vol.18(12), pp.1779-1783
Main Authors: ONO, Satoshi, YAMAFUJI, Tetsuo, CHAKI, Hisaaki, TODO, Yozo, MAEKAWA, Mutsuko, KITAMURA, Kazunori, KIMURA, Tatsuo, NAKADA, Yasushi, MOZUMI, Kuniko, NARITA, Hirokazu
Format: Article
Language:English
Subjects:
Animals
antiamnestic activity
Avoidance Learning - drug effects
basal forebrain lesion
Biological and medical sciences
cerebral embolism
cerebral monoamine
cognition enhancing agent
Diethylamines - therapeutic use
Diethylamines - toxicity
Hypoxia - drug therapy
Intracranial Embolism and Thrombosis - drug therapy
Lethal Dose 50
Male
Medical sciences
Mice
Neuropharmacology
Neurotransmitter Agents - metabolism
Nootropic Agents - therapeutic use
Pharmacology. Drug treatments
Prosencephalon - drug effects
Prosencephalon - physiopathology
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Rats
Rats, Wistar
Stereoisomerism
T-588
Thiophenes - therapeutic use
Thiophenes - toxicity
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Description
Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.18.1779