Effect of NIK-247 on Basal Concentrations of Extracellular Acetylcholinein the Cerebral Cortex of Conscious, Freely Moving Rats.

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We studied the effect of orally administered NIK-247 (9-amino-2, 3, 5, 6, 7, 8-hexahydro-1<I>H</I>-cyclopenta[<I>b</I>]quinoline monohydrochloride monohydrate) on basal extracellular acetylcholine (ACh) concentrations in the rat cerebral cortex using microdialysis without the addition of cholinesterase inhibitor to the perfusion fluid and radioimmunoassay for ACh. In addition, the effect of oral administration of NIK-247 on acetylcholinesterase (AChE) activity in rat cerebral cortex was determined. The mean basal ACh content in the perfusate from the cerebral cortex of freely moving rats was 123.2±21.8 fmol/30 min (n=7). NIK-247 (2.5 10.0 mg/kg, p.o.) increased the ACh content of the perfusate in a dose-dependent manner. NIK-247 at 10 mg/kg significantly increased the ACh content in the perfusate from 0.5 to 2.5 hr after administration, and the maximum increase was attained at 1 hr after administration. 9-Amino-1, 2, 3, 4-tetrahydroacridine (5 mg/kg, p.o.) and physostigmine (0.5 mg/kg, i.p.) significantly increased the ACh content in the perfusate from 1 to 2 hr and from 0.5 to 1.5 hr after administration, respectively. AChE activities in the cerebral cortex were about 32% and 12% below the control value at 1 hr and 3 hr after administration of NIK-247 at 10 mg/kg, respectively. These findings demonstrate that NIK-247 increases extracellular ACh concentration and inhibits AChE activity in the cerebral cortex after oral administration, and they suggest that NIK-247 facilitates central cholinergic transmission.
公益社団法人日本薬理学会の論文

Effect of NIK-247 on Basal Concentrations of Extracellular Acetylcholinein the Cerebral Cortex of Conscious, Freely Moving Rats.

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