Magnesium sulfate enhances non-depolarizing muscle relaxant vecuronium action at adult muscle-type nicotinic acetylcholine receptor in vitro

Abstract

Aim:To investigate the effect of magnesium sulfate and its interaction with the non-depolarizing muscle relaxant vecuronium at adult muscle-type acetylcholine receptors in vitro. Methods: Adult muscle-type acetylcholine receptors were expressed in HEK293 cells. Drug-containing solution was applied via a gravity-driven perfusion system. The inward currents were activated by brief application of acetylcholine (ACh), and recorded using whole-cell voltage-clamp technique. Results: Magnesium sulfate (1-100 mmol/L) inhibited the inward currents induced ACh (10 μmol/L) in a concentration-dependent manner (IC 50 =29.2 mmol/L). The inhibition of magnesium sulfate was non-competitive. In contrast, vecuronium produced a potent inhibition on the adult muscle-type acetylcholine receptor (IC 50 =8.7 nmol/L) by competitive antagonism. Magnesium sulfate at the concentrations of 1, 3, and 6 mmol/L markedly enhanced the inhibition of vecuronium (10 nmol/L) on adult muscle-type acetylcholine receptors. Conclusion: Clinical enhancement of vecuronium-induced muscle relaxation by magnesium sulfate can be attributed partly to synergism between magnesium sulfate and non-depolarizing muscle relaxants at adult muscle-type acetylcholine receptors.

In response to the letter by Carron et al. concerning the case report by Unterbuchner et al.

“…8 On the other hand, magnesium decreases the pre-junctional release of acetylcholine and diminishes the inward currents and the excitability of muscle membranes postjunctionally. 9 This was probably demonstrated by the reduction in normalised T1 to 25% in our case and T1 to 21% in Carron's case. 1,2 Interestingly, magnesium showed just a minor reduction in the TOF ratio in both cases (67% and 65%) maybe because of the lacking effect of relevant fractions of free muscle relaxant at the pre-junctional a 3 b 2 acetylcholinreceptors.…”

“…10 Nevertheless, the application of 1 g CaCl 2 may not neutralise the magnesium effect completely, because of its pre-junctional action. 2,9 Clinically, relevant muscle weakness can therefore persist temporarily. Also in Carron's case, neither T1 nor TOF ratio returned to baseline values in the observed period.…”

Magnesium‐induced recurarisation after reversal of rocuronium‐induced neuromuscular block with sugammadex

“…Magnesium itself directly diminishes the prejunctional release of acetylcholine. In combination with a possibly small amount of rocuronium at the acetylcholine receptors (AChR), this reduction could decrease normalised T1 to 25%, matching the effect of magnesium‐induced prolongation, particularly on clinical duration . Magnesium decreased the absolute level of all four twitches of the TOF series.…”

Dexmedetomidine vs. Magnesium Sulphate as an Adjuvant to Rocuronium Bromide, and Local Anaesthetic Mixture in Peribulbar Anaesthesia for Viteroretinal Surgery

“…MgSO 4 by acting as a calcium channel blocker at presynaptic level reduces acetylcholine release at the motor endplate, which lowers the excitability of the muscle and the amplitude of endplate potential, resulting in the augmentation of a neuromuscular blockade by NDMRs [13]. However, A study done by Wang H et al [28] found that this potentiation of NDMRs by magnesium can be in part due to a combined effect on adult muscle-type acetylcholine receptors.…”