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.
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.
Noda
Akihiro
A
Advanced Technology Platform Research Laboratory, Fuijsawa Pharmaceutical Co., Ltd. Ibaraki, Japan. anoda@mprcf.or.jp
Takamatsu
Hiroyuki
H
Matsuoka
Nobuya
N
Koyama
Satoshi
S
Tsukada
Hideo
H
Nishimura
Shintaro
S
D000375:Aging / Q000502:physiology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed / Q000379:methods
D001549:Benzamides; C102991:N-(4-acetyl-1-piperazinyl) -4-fluorobenzamide monohydrate; D010879:Piperazines; D005947:Glucose