Journal of Anesthesia

, Volume 32, Issue 6, pp 806–812 | Cite as

A new rocuronium formulation not causing vascular pain in a flexor reflex model of anesthetized rats

  • Keisuke JimboEmail author
  • Yutaka Itsuji
  • Erika Kubo
  • Masamichi Kumagai
  • Kuniharu Masui
  • Yoshiro Yamamura
Original Article



Intravenous administration of the brand formulation of rocuronium bromide, currently used as a muscle relaxant, has been associated with vascular pain accompanied by withdrawal movements of the arm and wrist. The purpose of this study was to identify the cause of vascular pain induced by the brand formulation and to develop a new rocuronium formulation, not causing vascular pain, using a vascular pain-evoked flexor reflex response model of anesthetized rats.


A rat flexor reflex model, monitored by electromyography, was used to evaluate a flexor reflex response as the index of vascular pain. A catheter for drug administration was inserted into the superficial caudal epigastric artery. A needle electrode was inserted into a muscle in the femoral area to obtain an electromyogram (EMG) value. The integrated EMG values obtained after the administration of each test drug were compared to the baseline value and quantified.


The acetate buffer contained in the solvent could cause flexor reflex response. Furthermore, the flexor reflex response increased in an acid concentration-dependent manner. Based on these results, we prepared a new rocuronium formulation using a low-acid-concentration buffer solution and found that it decreased the integrated EMG value in the rat model. The integrated EMG value acquired using the brand formulation was reduced by pretreatment with the TRPA1 channel inhibitor.


Our findings suggest that the high acid concentration in the brand formulation buffer solution is the cause of vascular pain. The rocuronium formulation developed using a low-acid-concentration buffer solution might help eliminate vascular pain in the clinic.


Rocuronium New formulation Pain on injection 



The authors thank Dr. Ichiro Uchida, M.D., Ph.D., and Professor John Robert Sneyd for helpful comments on the manuscript.

Compliance with ethical standards

Conflict of interest

All authors are employees of Maruishi Pharmaceutical Co., Ltd.

Supplementary material

540_2018_2557_MOESM1_ESM.pdf (26 kb)
Supplementary material 1 (PDF 27 KB)
540_2018_2557_MOESM2_ESM.pdf (30 kb)
Supplementary material 2 (PDF 31 KB)


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Copyright information

© Japanese Society of Anesthesiologists 2018

Authors and Affiliations

  • Keisuke Jimbo
    • 1
    Email author
  • Yutaka Itsuji
    • 1
  • Erika Kubo
    • 1
  • Masamichi Kumagai
    • 1
  • Kuniharu Masui
    • 1
  • Yoshiro Yamamura
    • 1
  1. 1.Pharmaceutical Research and Development DivisionMaruishi Pharmaceutical Co., LtdOsakaJapan

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