Isobolographic analysis of non-depolarising muscle relaxant interactions at their receptor site

European Journal of Pharmacology
Matthias PaulC Spencer Yost

Abstract

Administration of certain combinations of non-depolarising muscle relaxants produces greater than expected neuromuscular blockade. Synergistic effects may be explained by drug interactions with the postsynaptic muscle nicotinic acetylcholine receptor. To investigate this hypothesis, the adult mouse muscle nicotinic acetylcholine receptor (alpha(2)beta delta epsilon) was heterologously expressed in Xenopus laevis oocytes and activated by the application of acetylcholine (10 microM). The effects of five individually applied muscle relaxants and six combinations of structurally similar and dissimilar compounds were studied. Drug combinations containing equipotent concentrations of two agents were tested and dose-response curves were determined. All compounds tested alone and in combination produced rapid and readily reversible, concentration-dependent inhibition. Isobolographic and fractional analyses indicated additive interactions for all six tested combinations. These findings suggest that synergistic neuromuscular blocking effects, observed for the administration of certain combinations of muscle relaxants, do not result from purely postsynaptic binding events at the muscle nicotinic acetylcholine receptor, but rather from dif...Continue Reading

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Citations

Mar 7, 2003·European Journal of Pharmacology·M Alexandrina TimóteoP Correia-de-Sá
Jun 10, 2010·Korean journal of anesthesiology·Soo Il Lee
Jun 10, 2015·Antimicrobial Agents and Chemotherapy·Marcia F da SilvaAlejandro M Katzin
Dec 4, 2020·World Journal of Clinical Cases·Eun-A JangSeongheon Lee

Related Concepts

Acetilcolina Cusi
Metazoa
Neuromuscular Nondepolarizing Agents
Dose-Response Relationship, Drug
Drug Interactions
Electrophysiology (Science)
Flaxedil
Isoquinolines
Oocytes
Pancuronium Curamed

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