(+/-)-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.