Effect of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate, a novel acetylcholinesterase inhibitor, on spatial cognitive impairment induced by chronic cerebral hypoperfusion in rats.
It is of interest whether the acetylcholinesterase inhibitor, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147), can improve cognitive impairment caused by chronic cerebral ischemia in rats. Two weeks after four-vessel occlusion, apparent impairments of spatial retrieval memory were observed in the Morris water maze. Both TAK-147 at doses of 0.1, 0.3 and 1.0 mg/kg and donepezil at doses of 0.3 and 1.0 mg/kg significantly ameliorated ischemia-induced memory deficits dose-dependently, but tacrine had no appreciable effect. Furthermore, we demonstrate that the intensity of staining by 2,3,5-triphenyltetrazolium in the hippocampal and cortical slices was significantly decreased by ischemia (10 min anoxia/aglycemia), and that it was also significantly restored by treatment with TAK-147 and donepezil.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004396:Coloring Agents; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009924:Organ Culture Techniques; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000494:pharmacology; D013778:Tetrazolium Salts
D001552:Benzazepines; D002800:Cholinesterase Inhibitors; D004396:Coloring Agents; D007189:Indans; D018696:Neuroprotective Agents; D010880:Piperidines; D013778:Tetrazolium Salts; D013619:Tacrine; C009591:triphenyltetrazolium; C099872:TAK 147; D000077265:Donepezil