Non-depolarizing neuromuscular blocker; muscle relaxant

In a concentration-dependent manner, rocuronium decreased the indirectly elicited twitch tensions in all pretreated diaphragms (P <.01, n = 6) and normal (50% inhibitory concentration [IC(50)], 9.84 [9.64-10.04] μM, mean [95% confidence interval]) [1]. Rocuronium's ED95 for children and adults is nearly the same. Its half-life is shorter in children than in adults, and it functions similarly to vecuronium. It is easy to reverse rocuronium with standard dosages of cholinesterase-inhibiting medications [2]. The times for setting the maximum block, recovering the twitch height from 25% to 75%, and recovering the twitch height from 25% to 75% were 1.7 (32), 53 (19), and 20 (37) minutes, respectively [3].

Merely 8.7±5.7% (SD) and 6.0±2.8%, respectively, of the administered dosages of ORG 9426 and ORG 9616 were eliminated through the urine. On the other hand, cats without renal pedicle ligation excreted 35.7±12.2% and 46.8±9.7% of ORG 9616 into the bile, and 54.4±9.2% and 52.4±9.2% of an administered dosage of ORG 9426, respectively [4].

Enzyme-linked immunosorbent assay (ELISA)[5]
To examine cytokines secreted by fibroblasts treated with or without RB for 12 h, the method of ELISA was performed using antibodies for CXCL12, IL8, HGF and TGF-β.

Human EC TE-1 and ECA-109 cells, and Human fibroblast HS-27, TIG-1 and CRL-7815 cells, were cultured within DMEM and 1640, respectively, containing fetal bovine serum 10% and antibiotics. Fibroblasts were pre-treated with multiple conditions, then passaged and co-cultured with EC cells using μ-Slide 2 Well System. The treatment conditions of drug cells are as followed: RB (Rocuronium bromide) treated for 12 h with 10–320 μg/mL; human CXCL12 recombinant protein treated for 12 h with 10 μg/mL (RP-8658); rapamycin (500 nM for 8 h)[5].

0.3 mg/kg and 0.6 mg/kg
Cats

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The neuromuscular blocking effects and pharmacokinetics of ORG 9426, 1.5 mg/kg and ORG 9616, 1.2 mg/kg iv, two new nondepolarizing neuromuscular blocking drugs, were studied in 28 cats (i.e., 14 cats with each drug) with and without renal pedicle ligation. A gas chromatographic assay was used to determine the concentrations of ORG 9426 and ORG 9616 and its desacetyl metabolites in plasma, urine, bile, and liver. The duration of neuromuscular blockade of both drugs was not altered by ligation of renal pedicles. Plasma clearance of ORG 9426 was slower in cats with ligated renal pedicles (P less than 0.01). With ORG 9616, mean elimination half-life was slower and mean residence time longer in cats with renal pedicle ligation. Otherwise, there was no significant differences with any pharmacokinetic variables in cats with and without renal pedicle ligation. Only 8.7 +/- 5.7% (SD) and 6.0 +/- 2.8% of an injected dose of ORG 9426 and ORG 9616 was excreted into the urine, respectively. Conversely, 54.4 +/- 9.2% and 52.4 +/- 9.2% of an injected dose of ORG 9426 and 35.7 +/- 12.2% and 46.8 +/- 9.7% of ORG 9616 were excreted into the bile in cats without and with renal pedicle ligation, respectively. Finally, 21.3 +/- 6.5% and 33.5 +/- 15.6% of ORG 9426 and 14.0 +/- 3.2% and 18.1 +/- 5.6% of ORG 9616 were in the liver 6 h after injection in cats without and with renal pedicle ligation respectively. The authors were able to account for the biodisposition of 84.4% and 85.9% of an injected dose of ORG 9426 in cats without and with renal pedicle ligation respectively.[4]

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Xenograft mouse study[5]
Four-week-old female BALB/c nude mice were used for xenograft tumor experiments. The transplantation and drug administration were carried out in strict accordance with the International Committee's Guide for the Care and Use of Laboratory Animals. For xenograft tumor experiment, 5 × 106 TE-1 or ECA-109 cells mixed with matrix-gel were subcutaneously inoculated into the back of the right upper limb of nude mice (3 mice per group). For systematical administration, after 1 week subcutaneous inoculation, RB with different concentrations (0, 10 and 20 mg/kg) [23] were administrated with the nude mice every 2 days for additional 2 weeks. For local administration, the gradient concentrations of RB (0, 40 and 80 μg per mouse) were given in the connective tissue layer underneath the tumor every two days for additional 2 weeks. Then mice were executed with carbon dioxide asphyxia, xenograft tumors were measured and removed for histochemical analysis.
Immunohistochemistry (IHC) was used to detect the expression change of ATG5 and CXCL12 influenced by RB treatment in vivo, xenograft tumors and their adjacent tissues were fixed, embedded within paraffin, and sectioned routinely. Antibodies against ATG5 at 1:500 dilution and CXCL12 at 1:1000 dilution were used respectively.

[1]. Narimatsu E, Niiya T, Takahashi K, Pralidoxime inhibits paraoxon-induced depression of rocuronium-neuromuscular block in a time-dependentfashion. Am J Emerg Med. 2012 Jul;30(6):901-7.
[2]. Wicks TC. The pharmacology of rocuronium bromide (ORG 9426). AANA J. 1994 Feb;62(1):33-8.
[3]. Wierda JM, Kleef UW, Lambalk LM, The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular blocking agent, in patients anaesthetized with nitrous oxide, halothane and fentanyl. Can J Anaesth. 1991 May;38(4 Pt 1):430-5.
[4]. Khuenl-Brady K, Castagnoli KP, Canfell PC, The neuromuscular blocking effects and pharmacokinetics of ORG 9426 and ORG 9616 in the cat. Anesthesiology. 1990 Apr;72(4):669-74.
[5]. J Transl Med. 2023 Apr 8;21(1):248. doi: 10.1186/s12967-023-04081-y.

Rocuronium bromide is the organic bromide salt of a 5alpha androstane compound having 3alpha-hydroxy-, 17beta-acetoxy-, 2beta-morpholino- and 16beta-N-allyllyrrolidinium substituents. It has a role as a neuromuscular agent and a muscle relaxant. It is an organic bromide salt and a quaternary ammonium salt. It contains a rocuronium. It derives from a hydride of a 5alpha-androstane.
Rocuronium Bromide is the bromide salt form of rocuronium, an intermediate-acting quaternary aminosteroid with muscle relaxant property. Rocuronium bromide competitively binds to the nicotinic receptor at the motor end plate, and antagonizes acetylcholine binding, which results in skeletal muscle relaxation and paralysis.
An androstanol non-depolarizing neuromuscular blocking agent. It has a mono-quaternary structure and is a weaker nicotinic antagonist than PANCURONIUM.

C32H53N2O4.BR

609.68

608.31884

C, 63.04; H, 8.76; Br, 13.11; N, 4.59; O, 10.50

119302-91-9

143558-00-3; 119302-91-9 (bromide)

441351

Typically exists as white to off-white solids at room temperature

162-164°C

1.31

59.0

[Br-].O(C(C([H])([H])[H])=O)[C@@]1([H])[C@]([H])(C([H])([H])[C@@]2([H])[C@]3([H])C([H])([H])C([H])([H])[C@@]4([H])C([H])([H])[C@@]([H])([C@]([H])(C([H])([H])[C@]4(C([H])([H])[H])[C@@]3([H])C([H])([H])C([H])([H])[C@@]21C([H])([H])[H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H])O[H])[N+]1(C([H])([H])C([H])=C([H])[H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H]

OYTJKRAYGYRUJK-UHFFFAOYSA-M

InChI=1S/C32H53N2O4.BrH/c1-5-14-34(15-6-7-16-34)28-20-26-24-9-8-23-19-29(36)27(33-12-17-37-18-13-33)21-32(23,4)25(24)10-11-31(26,3)30(28)38-22(2)35;/h5,23-30,36H,1,6-21H2,2-4H3;1H/q+1;/p-1

[(2S,3S,5S,8R,9S,10S,13S,14S,16S,17R)-3-hydroxy-10,13-dimethyl-2-morpholin-4-yl-16-(1-prop-2-enylpyrrolidin-1-ium-1-yl)-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate;bromide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.41 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 2: 100 mg/mL (164.02 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)