新規ベンジルピリジン誘導体KW-6055の中枢コリン作動性神経系に及ぼす影響

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We examined the effect of KW 6055 (α-(<I>p</I>-butyrylamino-<I>o</I>-nitrobenzyl) pyridinel, which has antiamnesic activity, on the central cholinergic systems of rat frontal cortex using in vivo brain microdialysis. 1) KW-6055 (40, 160 mg/kg, p.o.) increased the extracellular level of ACh in normal rats (257 ± 23, 202 ± 24%). The stimulating effect of KW-6055 on ACh release was abolished by tetrodotoxin treatment, supporting that the released ACh was due to neuronal firing. Reserpine pretreatment decreased the effect of KW-6055, indicating that KW-6055 acted on cholinergic neurons through catecholaminergic neurons. 2) In basal forebrain-lesioned rats, KW-6055 (40 mg/kg, p.o.) significantly increased the extracellular level of ACh (251±22%) for more than 2 hr, which was longer than in normal rats. In conclusion, these results suggest that the stimulating activity on ACh release may be involved in the mechanism of the antiamnesic effects of KW-6055.
社団法人日本薬理学会の論文