Decamethonium is a partial agonist at the nicotinic acetylcholine receptor.
The efficacy of decamethonium as an agonist at the nicotinic acetylcholine receptor has never been determined. Here, we demonstrate how patch clamp recording during rapid perfusion of agonists to outside-out patches from BC3H-1 cells can be used to provide an unambiguous estimate of the efficacy of decamethonium. First, we obtain the decamethonium concentration-response relationship between 10 and 1,000 microM decamethonium. The maximum channel open probability is small (< 0.02) and occurs at about 100 microM. This suggests two alternative explanations: decamethonium is a poor agonist or decamethonium is an efficacious agonist but a potent channel blocker. To distinguish between these alternatives, we perfuse mixtures of decamethonium and acetylcholine to generate acetylcholine concentration-response curves in the presence of 30, 100, and 1,000 microM decamethonium. We use a model for activation and block of the acetylcholine receptor by both agonists to fit these data and determine the binding affinity, efficacy, and blocking affinity of decamethonium. We conclude that the efficacy of decamethonium is low, 0.016. Decamethonium is a true partial agonist.
Liu
Y
Y
Department of Anesthesiology, State University of New York, Stony Brook 11794-8480.
Dilger
J P
JP
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002999:Clone Cells; D003650:Decamethonium Compounds / Q000494:pharmacology*; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D051379:Mice; D010477:Perfusion; D011978:Receptors, Nicotinic / Q000187:drug effects*
D003650:Decamethonium Compounds; D007473:Ion Channels; D011978:Receptors, Nicotinic; D000109:Acetylcholine