Pseudophrynaminol: A potent noncompetitive blocker of nicotinic receptor-channels

• Published in: Biochemical pharmacology Vol. 53; no. 5; pp. 671 - 676
• Main Authors: Badio, Barbara, Garraffo, H.Martin, Padgett, William L., Greig, Nigel H., Daly, John W.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 07.03.1997; Elsevier Science
• Subjects: acetylcholinesterase; Adult; Animals; Biological and medical sciences; Cholinergic system; Cholinesterase Inhibitors - pharmacology; Humans; Indoles - pharmacology; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nicotinic Antagonists - pharmacology; nicotinic receptors; noncompetitive blockers; PC12 Cells; Pharmacology. Drug treatments; physostigmine; Physostigmine - pharmacology; pseudophrynamines; Pyrroles - pharmacology; Rats; Sodium - metabolism; Sodium Channels - drug effects; nicotinic receptors; acetylcholinesterase; physostigmine; pseudophrynamines; noncompetitive blockers; Endocrinopathy; Pheochromocytoma; Rat; Esterases; Ionic channel; Acetylcholinesterase; Secretory tumor; Cholinergic receptor; Alkaloid; Guinea pig; Established cell line; Antagonist; Nicotinic receptor; Tumor cell; Human; Enzyme; Rodentia; In vitro; Carboxylic ester hydrolases; Vertebrata; Synapse; Mammalia; Neuron; Sodium; Animal; Hydrolases; Non competitive inhibition
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(96)00878-7

(±)-Pseudophrynaminol inhibited carbamylcholine-elicited sodium-22 influx with an IC 50 value of about 0.3 μM 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 μM) for the agonist site on central nicotinic receptors at which [ 3H]nicotine binds. Pseudophrynaminol, at 10 μM, had marginal effects on a variety of other central receptors, and even at 100 μM inhibited batrachotoxin-elicited sodium-22 influx in a synaptoneurosomal preparation by only 40%. It had no effect at 30 μM 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.