Pseudophrynaminol: A potent noncompetitive blocker of nicotinic receptor-channels

被引:18
作者
Badio, B
Garraffo, HM
Padgett, WL
Greig, NH
Daly, JW
机构
[1] NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892
[2] NIA,NEUROSCI LAB,BALTIMORE,MD 21224
关键词
pseudophyrnamines; nicotinic receptors; physostigmine; noncompetitive blockers; acetylcholinesterase;
D O I
10.1016/S0006-2952(96)00878-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
(+/-)-Pseudophrynaminol inhibited carbamylcholine-elicited sodium-22 influx with an IC50 value of about 0.3 mu M in both rat pheochromocytoma PC12 cells (ganglionic-type nicotinic receptor) and human medulloblastoma TE671 cells (neuromuscular-type nicotinic receptor). The inhibition in both cell lines appeared to be noncompetitive in nature. In rat cerebral cortical membranes, pseudophrynaminol had only low affinity (K-i 35 mu M) for the agonist site on central nicotinic receptors at which [H-3]nicotine binds. Pseudophrynaminol, at 10 mu M, had marginal effects on a variety of other central receptors, and even at 100 mu M inhibited batrachotoxin-elicited sodium-22 influx in a synaptoneurosomal preparation by only 40%. It had no effect at 30 mu M on acetylcholinesterase and was a weak inhibitor of butyrylcholinesterase. Thus, pseudophrynaminol appears to be a potent, rather specific, noncompetitive inhibitor of ganglionic and neuromuscular nicotinic receptor-channels. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:671 / 676
页数:6
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