Rocuronium Has a Suppressive Effect on Platelet Function via the P2Y12 Receptor Pathway In Vitro That Is Not Reversed by Sugammadex.

Yutaka Murata,Kazuhiko Fukuda,Shuji Kawamoto

doi:10.3390/ijms21176399

Yutaka Murata, Kazuhiko Fukuda + Show 1 more

Open Access

https://doi.org/10.3390/ijms21176399

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Abstract

Rocuronium is an aminosteroid nondepolarizing neuromuscular blocker that is widely used for anesthesia and intensive care. In this study, we investigated the effect of rocuronium on human platelet functions in vitro. The effects of rocuronium on platelet aggregation, P-selectin expression, and cyclic adenosine monophosphate (cAMP) levels in platelets were measured using an aggregometer, an enzyme immunoassay, and flow cytometry, respectively. Rocuronium inhibited ADP-induced platelet aggregation, P-selectin expression and suppression of cAMP production. These effects were not antagonized by equimolar sugammadex, a synthetic γ-cyclodextrin derivative that antagonizes rocuronium-induced muscle relaxation by encapsulating the rocuronium molecule. Morpholine, which constitutes a part of the rocuronium molecule but is not encapsulated by sugammadex, inhibited ADP-induced platelet aggregation. Vecuronium, which has a molecular structure similar to that of rocuronium but does not possess a morpholine ring, had no significant effect on ADP-induced platelet aggregation. These results indicate that rocuronium has a suppressive effect on platelet functions in vitro that is not reversed by sugammadex and suggest that this effect is mediated by blockade of the P2Y12 receptor signaling pathway via the morpholine ring of rocuronium.

Highlights

Platelets are anucleate cells that play a central role in thrombus formation in blood
The structures of rocuronium, vecuronium, the rocuronium/sugammadex complex, and morpholine are shown in Figure 1 [10]
Our study shows that the inhibitory effects of rocuronium on adenosine diphosphate (ADP)-induced platelet aggregation and P-selectin expression were not antagonized by equimolar sugammadex, which may suggest that rocuronium suppresses platelet functions via its morpholine ring, because this ring is not encapsulated by sugammadex [8,10]

Summary

Introduction

Platelets are anucleate cells that play a central role in thrombus formation in blood. Information on the effects of perioperative drugs, including anesthetics, on platelet function is important for patient care. We have described the effects on platelets of various anesthetics used during the perioperative period [1,2,3,4,5,6,7], but the effects on human platelets of many drugs used perioperatively remain to be clarified. Rocuronium ((+)-(17β-acetoxy-3α-hydroxy-2β-morpholino-5α-androstan-16β-yl)-1-allyl-1-pyrrolidinium bromide), an aminosteroid nondepolarizing neuromuscular blocker, is widely used for anesthesia and intensive care [8], but its effect on human platelet functions has not been examined. Sugammadex shows a similar effect against vecuronium, another widely used aminosteroid nondepolarizing neuromuscular blocker. The molecular structure of vecuronium resembles that of rocuronium but does not have a morpholine ring. The structures of rocuronium, vecuronium, the rocuronium/sugammadex complex, and morpholine are shown in Figure 1 [10]

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Discussion

Conclusion