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NEUROPHARMACOLOGY

Effect of N-(4-Acetyl-1-piperazinyl)-p-fluorobenzamide Monohydrate (FK960), an Antidementia Drug with a Novel Mechanism of Action, on Regional Cerebral Blood Flow and Glucose Metabolism in Aged Rhesus Macaques Studied with Positron Emission Tomography

Advanced Technology Platform Research Laboratory, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan (A.N., S.N.); Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan (H.T., N.M.); Development Division, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan (S.K.); Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka, Japan (H.T.); Department of Biotracer Medicine, Kanazawa University Graduate School of Medical Sciences, Ishikawa, Japan (A.N.); and The Medical and Pharmacological Research Center Foundation, Ishikawa, Japan (A.N., H.T., S.N.)

Effect of N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate (FK960), a putative antidementia drug with a novel mechanism of action, on regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose (rCMRglc) was examined in conscious aged rhesus macaques using positron emission tomography. Seven aged (21.6 ± 2.7 years) male rhesus macaques were subjected. FK960 was intramuscularly administered at doses of 0, 0.01, 0.1, or 1 mg/kg for seven consecutive days, in randomized order and in a blinded manner. Each subject was scanned four times in all, with at least 3-week intervals, after treatment with saline or three doses of FK960. Significant increases in rCBF in the left temporal and left frontal cortex, and in rCMRglc in the right hippocampus with adjacent cortex, were observed in the treatment group with 1 mg/kg FK960, without affecting any other cardiovascular and respiratory variables. No statistically significant change in any region was observed at doses of 0.01 or 0.1 mg/kg. These results suggested that FK960 restored the rCBF and rCMRglc deficits in brain areas responsible for cognitive functioning in aged rhesus macaques.

Address correspondence to: Akihiro Noda, The Medical and Pharmacological Research Center Foundation, Wo-32, Inoyama-machi, Hakui, Ishikawa 925-0613, Japan. E-mail: anoda{at}mprcf.or.jp