title: Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium.
abstract: Three clinically used anticholinesterases--neostigmine, pyridostigmine, and edrophonium--were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED50 for 95% block 5.5 +/- 4 nM), followed by pyridostigmine (0.27 +/- 0.06 microM) and edrophonium (2.1 +/- 0.05 microM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004491:Edrophonium / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009388:Neostigmine / Q000494:pharmacology*; D009407:Nerve Block; D010197:Pancuronium / Q000037:antagonists & inhibitors*; D010791:Phrenic Nerve / Q000187:drug effects; D011729:Pyridostigmine Bromide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D009388:Neostigmine; D004491:Edrophonium; D010197:Pancuronium; D011729:Pyridostigmine Bromide