Special Articles  |   May 2017
Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D.
Author Notes
  • From the Department of Anaesthesia and Intensive Care, Midcentral Health, Palmerston North, New Zealand (N.A.P., R.G.M.); and Department of Medical Education and Clinical Research, Saint Barnabas Medical Center, Livingston, New Jersey (H.R.).
  • Corresponding article on page 759.
    Corresponding article on page 759.×
  • Submitted for publication August 18, 2016. Accepted for publication January 26, 2017.
    Submitted for publication August 18, 2016. Accepted for publication January 26, 2017.×
  • Address correspondence to Dr. Pollock: Department of Anaesthesia and Intensive Care, Midcentral Health, Private Bag, Palmerston North, New Zealand. neilp@midcentraldhb.govt.nz. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Special Articles / Neuromuscular Diseases and Drugs / Pharmacology
Special Articles   |   May 2017
Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D.
Anesthesiology 5 2017, Vol.126, 774-779. doi:10.1097/ALN.0000000000001596
Anesthesiology 5 2017, Vol.126, 774-779. doi:10.1097/ALN.0000000000001596
Abstract

Dantrolene—a nitrofurantoin derivative—was developed by Snyder et al. in 1967. After initial discovery of its muscle relaxation potential, investigations in a number of species demonstrated dose-dependent reductions in skeletal muscle tone that were long lasting, relatively nontoxic, and free of adverse effects such as respiratory impairment. Ellis et al. then published a number of papers investigating the means by which dantrolene produced these effects. Using a series of classic physiologic models, Ellis investigated potential sites of action for the new drug, eventually narrowing this down to the intracellular calcium-release mechanism. Ellis went on to play a pivotal role in the discovery of dantrolene’s effectiveness for the treatment of malignant hyperthermia, after reading a scientific bulletin about muscle rigidity in pigs affected by porcine stress syndrome, contacting Gaisford Harrison and sending dantrolene to him for trial.