[Effects of KW-6055, a novel benzylpyridine derivative, on central cholinergic systems].
We examined the effect of KW-6055 [alpha-(p-butyrylamino-o-nitrobenzyl) pyridine], which has anti-amnesic 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 anti-amnesic effects of KW-6055.
Kurokawa
M
M
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Mori
A
A
Shiozaki
S
S
Kanda
T
T
Yoshizaki
R
R
Ishii
A
A
D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000647:Amnesia / Q000188:drug therapy; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009578:Nitrobenzenes / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D012110:Reserpine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013779:Tetrodotoxin / Q000494:pharmacology
C076951:2-(4-butyrylamino-2-nitrobenzyl)pyridine; D009578:Nitrobenzenes; D011725:Pyridines; D011976:Receptors, Muscarinic; D013779:Tetrodotoxin; D012110:Reserpine; D000110:Acetylcholinesterase; D000109:Acetylcholine