Effects of T-82, a novel acetylcholinesterase inhibitor, on impaired learning and memory in passive avoidance task in rats.
Effects of 2-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dihydro-9-methoxy-1H-pyrrolo[3,4-b]quinolin-1-one hemifumarate (T-82), a new quinoline derivative, on drug- and basal forebrain lesion-induced amnesia models were examined in rats. Scopolamine (0.5 mg/kg, i.p.) and cycloheximide (1.5 mg/kg, s.c.) shortened the step-through latency in the passive avoidance task. T-82 significantly ameliorated amnesia induced by scopolamine or cycloheximide at the dose of 0.03, 0.1 and 0.3 mg/kg, p.o., and 0.3 and 1.0 mg/kg, p.o., respectively. Basal forebrain lesions with ibotenic acid shortened the step-through latency in passive avoidance task. An acute (0.1 and 0.3 mg/kg, p.o.) or subacute (0.03-0.3 mg/kg, p.o., for 7 days) treatment of T-82 significantly reversed the shortened latency. These results suggest that T-82 may ameliorate the impairment of memory induced by acetylcholinergic dysfunction.
Isomae
Kazuo
K
Central Research Laboratories, SSP Co Ltd, 1143 Nanpeidai, Narita, Chiba 286-8511, Japan. Kazuo.Isomae@ssp.co.jp
Morimoto
Shinichi
S
Hasegawa
Hiroshi
H
Morita
Kayo
K
Kamei
Junzo
J
D000647:Amnesia / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005650:Fumarates / Q000494:pharmacology*; D007051:Ibotenic Acid / Q000008:administration & dosage; D007859:Learning Disabilities / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008568:Memory / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects / Q000293:injuries; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
C475637:2-(2-(1-benzylpiperidin-4-yl)ethyl)-2,3-dihydro-9-methoxy-1H-pyrrolo(3,4-b)quinolin-1-one hemifumarate; D002800:Cholinesterase Inhibitors; D005650:Fumarates; D011500:Protein Synthesis Inhibitors; D011804:Quinolines; D007051:Ibotenic Acid; D003513:Cycloheximide; D012601:Scopolamine