Interaction among Agents that Block End-plate Depolarization Competitively

Waud, B. E.; Waud, D. R.; Phil, D.

doi:10.1097/00000542-198507000-00002

Cited by 38 publications

(17 citation statements)

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“…It could also reflect the potentiation between depolarizing and nondepolarizing drugs previously reported for other neuromuscular blocking drugs (11)(12)(13)(14)(15)(16). There are multiple processes in neuromuscular transmission susceptible to interactions between depolarizing and nondepolarizing drugs including effects on presynaptic receptors (17), postsynaptic receptors (18), and acetylcholinesterase activity (19).…”

Section: Discussionmentioning

confidence: 99%

Effects of Succinylcholine on the Pharmacodynamics of Pipecuronium and Pancuronium

Dubois

Fleming

Lea

1991

Anesthesia & Analgesia

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To study the effects of succinylcholine on subsequent pharmacodynamics of nondepolarizing muscle relaxants, a comparative pharmacodynamic study was carried out in patients having balanced anesthesia (thiopental, fentanyl, nitrous oxide/oxygen) in whom equipotent doses of pipecuronium (80 micrograms/kg) and pancuronium (100 micrograms/kg) were given with or without prior administration of succinylcholine (1 mg/kg). Fifty-two patients were randomly assigned to one of the following four groups: 1, pancuronium (100 micrograms/kg); 2, pipecuronium (80 micrograms/kg); 3, succinylcholine (1 mg/kg) plus pancuronium (100 micrograms/kg); and 4, succinylcholine (1 mg/kg) plus pipecuronium (80 micrograms/kg). In groups 3 and 4, the nondepolarizing relaxant was given after succinylcholine when the twitch height recovered to 75% of its control value. For maintenance of neuromuscular blockade, additional increments of pancuronium (20 micrograms/kg) or pipecuronium (15 micrograms/kg) were given. Neuromuscular function was monitored throughout induction, maintenance, spontaneous recovery, and pharmacologic reversal of the neuromuscular block. Mean onset times for pancuronium (group 1) and pipecuronium (group 2) given without succinylcholine were (mean +/- SEM) 2.5 +/- 0.3 and 2.8 +/- 0.2 min, respectively. Mean onset times (times to maximum twitch depression) of the two drugs given after succinylcholine (groups 3 and 4) were significantly shorter (1.4 +/- 0.4 and 1.6 +/- 0.1 min, respectively). Clinical durations (i.e., until 25% twitch recovery of pancuronium and pipecuronium) were not significantly different among the four groups, varying from 81.1 +/- 5.4 (group 4) to 107.0 +/- 17.0 (group 2) min.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Effects of Succinylcholine on the Pharmacodynamics of Pipecuronium and Pancuronium

Dubois

Fleming

Lea

1991

Anesthesia & Analgesia

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“…In contrast to the previous report (Paul et al, 2002), our measurements were made under conditions of high receptor inhibition by one or both antagonists. This provides a more sensitive test for synergistic effects (Nigrovic and Amann, 2004; Waud and Waud, 1985). Previously, we used this approach in a study of adult human nAChR (Liu and Dilger, 2008) and found evidence for synergy; in some cases, synergy at the receptor level correlated with the clinical phenomenon of muscle relaxant synergy in which pairs of antagonist are more effective at inducing paralysis than expected from their individual potencies (Lebowitz et al, 1980; Waud and Waud, 1984).…”

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confidence: 99%

Site Selectivity of Competitive Antagonists for the Mouse Adult Muscle Nicotinic Acetylcholine Receptor

Liu

Dilger

2008

Mol Pharmacol

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The muscle-type nicotinic acetylcholine receptor has two nonidentical binding sites for ligands. The selectivity of acetylcholine and the competitive antagonists (ϩ)-tubocurarine and metocurine for adult mouse receptors is known. Here, we examine the site selectivity for four other competitive antagonists: cisatracurium, pancuronium, vecuronium, and rocuronium. We rapidly applied acetylcholine to outside-out patches from transfected BOSC23 cells and measured macroscopic currents. We have reported the IC 50 of the antagonists individually in prior publications. Here, we determined inhibition by pairs of competitive antagonists. At least one antagonist was present at a concentration producing Ն67% receptor inhibition. Metocurine shifted the apparent IC 50 of (ϩ)-tubocurarine in quantitative agreement with complete competitive antagonism. The same was observed for pancuronium competing with vecuronium.However, pancuronium and vecuronium each shifted the apparent IC 50 of (ϩ)-tubocurarine less than expected for complete competition but more than expected for independent binding. The situation was similar for cisatracurium and (ϩ)-tubocurarine or metocurine. Cisatracurium did not shift the apparent IC 50 of pancuronium or vecuronium, indicating independent binding of these two pairs. The data were fit to a two-site, two-antagonist model to determine the antagonist binding constants for each site, L ␣ and L ␣␦ . We found L ␣ /L ␣␦ ϭ 0.22 (range, 0.14 -0.34), 20 (9 -29), 21 (4 -36), and 1.5 (0.3-2.9) for cisatracurium, pancuronium, vecuronium, and rocuronium, respectively. The wide range of L ␣ /L ␣␦ for some antagonists may reflect experimental uncertainties in the low affinity site, relatively poor selectivity (rocuronium), or possibly that the binding of an antagonist at one site affects the affinity of the second site.

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“…In addition to aforementioned mechanism of potentiation, Waud and Waud reported that this potentiation could also be observed even in the experiments which eliminated the pre-synaptic component by the use of externally administered agonist (carbachol) 14. This findings suggested the involvement of some other mechanisms of the potentiation.…”

Section: Discussionmentioning

confidence: 93%

Interactions between ORG9426 and other non-depolarizing neuromuscular blocking agents in ratsin vivo

Watanabe

1992

J Anesth

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In this study, combined neuromuscular blocking effects of ORG9426 with other non-depolarizing neuromuscular blocking agents were investigated. About 20% steady state neuromuscular block was established by a continuous infusion of one of 6 neuromuscular blocking agents (ORG9426, vecuronium, pancuronium, pipecuronium, d-tubocurarine and metocurine). Then 1/7 of the ED50 of ORG9426 or one of other neuromuscular blocking agents was administered in a single injection, and the increase in the neuromuscular block was observed. The combined neuromuscular blocking effect of ORG9426 and d-tubocurarine or ORG9426 and metocurine was significantly ( P < 0.05) greater than that of each corresponding control (the combination of same neuromuscular blocking agent). The effect of d-tubocurarine was also potentiated by vecuronium, pancuronium and pipecuronium. These potentiations were not observed between ORG9426 and pancuronium, pipecuronium or vecuronium. Possible mechanisms of these synergistic interactions were discussed.

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Interaction among Agents that Block End-plate Depolarization Competitively

Cited by 38 publications

References 0 publications

Effects of Succinylcholine on the Pharmacodynamics of Pipecuronium and Pancuronium

Effects of Succinylcholine on the Pharmacodynamics of Pipecuronium and Pancuronium

Site Selectivity of Competitive Antagonists for the Mouse Adult Muscle Nicotinic Acetylcholine Receptor

Interactions between ORG9426 and other non-depolarizing neuromuscular blocking agents in ratsin vivo

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