Ipidacrine (NIK-247), a novel antidementia, rapidly enters the brain and improves scopolamine-induced amnesia in rats during the Morris water maze task.
The effects of single and repeated administrations of ipidacrine (NIK-247, 9-amino-2, 3, 5, 6, 7, 8-hexahydro-1H-cyclopenta [b] quinoline monohydrochloride monohydrate) on scopolamine-induced spatial learning deficit were investigated in rats using the Morris water maze task. A single oral administration of ipidacrine (0.3 and 1 mg/kg) reduced the increased total latency induced by scopolamine in this task. The repeated administration of ipidacrine (1 mg/kg) of once a day for 5 successive days reduced the increased total latency induced by scopolamine to the levels of the saline-treated control rats in this task. In this pharmaco-kinetic study, ipidacrine was rapidly taken up into the brain within 5 min. Moreover, higher drug levels were observed mainly in the cortex and hippocampus, which both play important roles in learning and memory. Thus, a previous study together with this investigation indicate that ipidacrine improves amnesia which consists of the impairment of the working and reference memory in various animal models, suggesting that ipidacrine is a useful candidate for the therapy of patients with Alzheimer's disease.
Onodera
K
K
Department of Pharmacology, Tohoku University School of Dentistry, Sendai, Japan.
Kojima
J
J
Wachi
M
M
D000634:Aminoquinolines / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D002800:Cholinesterase Inhibitors; D008401:Gas Chromatography-Mass Spectrometry; D006624:Hippocampus / Q000378:metabolism; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D011619:Psychotropic Drugs / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D011619:Psychotropic Drugs; C049860:amiridine; D012601:Scopolamine