title: ADMET considerations when prescribing novel therapeutics to treat restless legs syndrome.
abstract: BACKGROUND
  Restless legs syndrome (RLS) is a commonly occurring sensory motor disorder that might impair nocturnal rest causing decreased alertness, depression, reduced job performance and poor quality of life. In patients affected by severe RLS, a pharmacological treatment is mandatory.
  
  
  METHODS
  The present review is based on a search using PubMed from 1994 to 2014. It is focused on the Absorption, Distribution, Metabolism, Elimination and Toxicology (ADMET) characteristics of drugs currently used and under development for the treatment of RLS.
  
  
  CONCLUSIONS
  The drugs currently available for RLS treatment do not always provide an optimal control of symptoms. There is still need for effective and well-tolerated new drugs. Long-acting dopamine agonists showed better efficacy than short-acting compounds in the treatment of severe RLS. There seems to be an inverse relationship between the half-life of the compound and the development of augmentation. Monoamine oxidase B inhibitors could be good candidates for initial treatment of RLS, sparing stronger dopaminergic agents for later stages of the disease. Oxycodone-naloxone demonstrated a significant and sustained treatment effect for patients with severe RLS insufficiently treated with first-line drugs and could be used as a long-term treatment in severe RLS when alternative satisfactory drug regimens are unavailable.
authors.affiliation: University of Udine Medical School, Department of Experimental and Clinical Medical Sciences, Neurology Unit , Udine , Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: de Biase
authors.forename: Giovanni
authors.initials: G
authors.lastname: Merlino
authors.forename: Simone
authors.initials: S
authors.lastname: Lorenzut
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Valente
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gigli
mesh_terms: D000818:Animals; D018491:Dopamine Agonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D004338:Drug Combinations; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D009270:Naloxone / Q000627:therapeutic use; D010098:Oxycodone / Q000627:therapeutic use; D011788:Quality of Life; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D018491:Dopamine Agonists; D004338:Drug Combinations; D008996:Monoamine Oxidase Inhibitors; C557247:oxycodone naloxone combination; D009270:Naloxone; D010098:Oxycodone
keywords: absorption; augmentation; distribution; dopamine; elimination; metabolism; monoamine oxidase B inhibitors; oxycodone-naloxone; pharmacokinetic; toxicology