• Anesthesiology · May 2017

    Biography Historical Article

    Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D.

    • Neil A Pollock, Roslyn G Machon, and Henry Rosenberg.
    • 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 C... more enter, Livingston, New Jersey (H.R.). less
    • Anesthesiology. 2017 May 1; 126 (5): 774-779.

    AbstractDantrolene-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.

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