title: Early Development, Identification of Mode of Action, and Use of Dantrolene Sodium: The Role of Keith Ellis, Ph.D.
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.
authors.affiliation: 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.).
authors.forename: Neil A
authors.initials: NA
authors.lastname: Pollock
authors.forename: Roslyn G
authors.initials: RG
authors.lastname: Machon
authors.forename: Henry
authors.initials: H
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D003620:Dantrolene / Q000266:history*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D008297:Male; D009125:Muscle Relaxants, Central / Q000266:history*; D014481:United States
chemical_list: D009125:Muscle Relaxants, Central; D003620:Dantrolene