Control pigs required 109.9 ug/kg/min and MHS pigs required 72.4 ug/kg/min infusion of Organon 9426 to maintain a 90% block. It appears that Organon 9426 is only one-third to one-half as potent as Vecuronium in pigs. The fact that MHS pigs only require 66% of the infusion dose to maintain a 90% block suggests that there is difference in the neuromuscular effect of Organon 9426 in MHS vs. control pigs. A linear regression analysis of the dose response data to Organon 9426 in MHS pigs indicated that 427.033 ug/kg would be required to produce a 100% neuromuscular blockade vs. 586.31 ug/kg in control pigs. Nine of the ten MHS pigs did not develop MH or show any signs of impending MH during the halothane and succinylcholine challenge at the end of the infusion period. Organon 9426 is the first muscle relaxant to offer significant protective action at a clinical dose. This suggests that there is an allosteric site on the sodium channel (acetylcholine receptor) which regulates the flow of sodium ions through the sodium channel. Organon 9426 may be therapeutically effective in an active MH case [1].
References
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Williams, C.H. (2015) Malignant Hyperthermia: Organon 9426 Was Evaluated in 10 MHS Pigs and 8 Control Pigs. Presented at EB2015 Boston, 1 April 2015, as FASEBJ 29: Abstract W109, #1039.1.
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[10]
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Williams, C.H., Hoech, G.P. and Zukaitis, M.G. (2014) A Review of the Factors Affecting the Incidence of Malignant Hyperthermia in the Greater Kansas City Area. Advances in Bioscience and Biotechnology, 5, 452-461. http://dx.doi.org/10.4236/abb.2014.55055
[14]
Williams, C.H., Dozier, S.E., Ilias, W.K., Fulfer, R.T., Zukaitis, M.G. and Hoech, G.P. Diltiazem and Malignant Hyperthermia. Submitted to Anesthesia and Analgesia.
[15]
Williams, C.H., Dozier, S.E. and Shanklin, M.D. (1986) Metabolic Rate in Malignant Hyperthermia Susceptible (MHS) Pigs. In: Tumbleson, M.E., Ed., Swine in Biomedical Research, Plenum, New York, 573-584.
[16]
Williams, C.H. (2014) Malignant Hyperthermia: A Runaway Thermogenic Futile Cycle at the Sodium Channel Level. Advances in Bioscience and Biotechnology, 5, 197-200. http://dx.doi.org/10.4236/abb.2014.53025
[17]
Williams, C.H. (2015) Malignant Hyperthermia: Organon 9426 Was Evaluated in 10 MHS Pigs and 8 Control Pigs. FASEB J, 29, 1.1039.1.
