Characterization of neuromuscular blocking action of piperidine derivatives.
cis and trans forms of 2-methyl-6-n-undecyl piperidines (C-11) are the main constituents of fire ant venom and have been studied for their mechanism of action on the neuromuscular transmission of the nerve-sartorius muscle preparation of frogs. At low concentrations (l times 10(-6)-2 times 10(-5) M), cis- and trans-C-11 irreversibly decreased the amplitude of spontaneous miniature end-plate potentials nerve-evoked end-plate potentials and iontophoretically induced acetylcholine depolarizations without changing the membrane potential. The quantal content and the focally recorded action potentials of nerve terminals remain unchanged. It was concluded that the piperidine derivatives block neuromuscular transmission postsynaptically through a decrease in the sensitivity of the end-plate membrane to acetylcholine. Pretreatment of the end-plate with d-tubocurarine did not effect the blocking action of trans-C-11. In direct binding experiments, trans-C-11 did not compete for the sites occupied by alpha-bungarotoxin, decamethonium, carbamylcholine and d-tubocurarine. These data suggest that trans-C-11 does not bind to the acetylcholine receptor site where the other cholinergic ligands have their affinity. It appears that these piperidine derivatives interfere with the coupling mechanism between acetylcholine-receptor binding and ionic conductance increases.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D004347:Drug Interactions; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011894:Rana pipiens; D011950:Receptors, Cholinergic; D009435:Synaptic Transmission / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology
D002038:Bungarotoxins; D009466:Neuromuscular Blocking Agents; D010880:Piperidines; D011950:Receptors, Cholinergic; D000109:Acetylcholine; D014403:Tubocurarine