title: The pharmacology of medieval sedatives: the "Great Rest" of the Antidotarium Nicolai.
abstract: BACKGROUND
  Past practices of compound drugs from different plant ingredients enjoyed remarkable longevity over centuries yet are largely dismissed by modern science as subtherapeutic, lethal or fanciful.
  
  
  OBJECTIVE
  To examine the phytochemical content of a popular medieval opiate drug called the "Great Rest" and gauge the bioavailability and combined effects of its alkaloid compounds (morphine, codeine, hyoscyamine, scopolamine) on the human body according to modern pharmacokinetic and pharmacodynamic parameters established for these compounds.
  We reviewed the most recent studies on the pharmacodynamics of morphine, codeine, hyoscyamine and scopolamine to ascertain plasma concentrations required for different physiological effects and applied these findings to dosage of the Great Rest.
  
  
  RESULTS
  Given the proportional quantities of the alkaloid rich plants, we calculate the optimal dose of Great Rest to be 3.1±0.1-5.3±0.76 g and reveal that the lethal dose of Great Rest is double the therapeutic concentration where all three alkaloid compounds are biologically active.
  
  
  CONCLUSIONS
  This study helps establish the effective dose (ED50), toxic dose (TD50) and lethal dose (LD50) rates for the ingestion of raw opium, henbane and mandrake, and describes their probable combined effects, which may be applied to similar types of pre-modern pharmaceuticals to reveal the empirical logic behind past practices.
authors.affiliation: History Dept and Centre for Medieval Studies University of Toronto, 100 St. George Street, Toronto, ON, Canada M5S 3G3. Electronic address: n.everett@utoronto.ca.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Everett
authors.affiliation: Department of Pharmacology and Toxicology University of Toronto Medical Sciences Building, Rm 4207, 1 King׳s College Circle, Toronto, ON, Canada M5S 1A8. Electronic address: martino.gabra@mail.utoronto.ca.
authors.forename: Martino
authors.initials: M
authors.lastname: Gabra
mesh_terms: D000470:Alkaloids / Q000008:administration & dosage* / Q000266:history / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000266:history / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D049691:History, Medieval; D006801:Humans; D032304:Hyoscyamus / Q000737:chemistry; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000266:history / Q000494:pharmacology; D026781:Mandragora / Q000737:chemistry; D009892:Opium / Q000008:administration & dosage / Q000266:history / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D009892:Opium
keywords: Alkaloids; Codeine (PubChem CID: 5284371); Dosage; Medieval medicine; Morphine (Pubichem CID: 5288826); Opium; Scopolamine (PubChem CID: 5184); Sedatives; l-hyoscyamine (PubChem CID: 154417)