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

Abstract

ABSTRACT-We studied the effect of orally administered 3,5,6,7,quinoline monohydrochloride monohydrate) on basal extracellular acetylcholine (ACh) con centrations 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 con tent 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 con tent 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 32070 and 1207o 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.

Ipidacrine (NIK‐247): A Review of Multiple Mechanisms as an Antidementia Agent

“…and tacrine (5 mg/kg p.o.) increased extracellular acetylcholine concentration in the cerebral cortex, as measured by microdialysis technique (27). The degree of increase induced by ipidacrine at 10 mg/kg was almost equal to that induced by tacrine at 5 mg/kg (27).…”

“…Ipidacrine at 10 mg/kg p.o. significantly inhibited AChE activity in rat cerebral cortex 0.5,1, and 3 h after oral administration of ipidacrine (27). Compared with in vitro tests, it is very difficult to exactly assess the inhibitory effects of reversible AChE inhibitors on brain AChE activity ex vivo, since the inhibitory effects reverse rapidly when preparing the tissue for assay (21,60,68).…”