title: The preclinical discovery of lofexidine for the treatment of opiate addiction.
abstract: BACKGROUND
  Lofexidine is one therapeutic option used for treating the onslaught of sympathetic outflow that typically commences upon induction of opiate withdrawal. It was approved for opiate detoxification in the UK, most of EU, and a select few countries worldwide during the 1980s and the 90s. Within the US and Canada, however, it remains an experimental drug.
  
  
  METHODS
  The following article highlights lacunae in extant knowledge about the molecular pharmacology of lofexidine. Furthermore, the article provides a brief discussion on the nature and shortcomings of clinical trials for this drug that have been conducted over the past 30 years across the world. It also provides a discussion of the market factors and regulatory considerations responsible for the rather limited use of lofexidine thus far.
  
  
  CONCLUSIONS
  Many lessons can be learned from the 40-year-long development of lofexidine. Indeed, unless there is an urgent need to address an unmet and/or immediate health threat, preclinical development is dictated by pharmacoeconomic considerations. Lofexidine would likely have been excluded for further development in this day and age given the existence and value of clonidine as well as the lack of insurance coverage for opiate addiction. It should be noted, however, that although there have been many oversights in the past, current experimentation and clinical trials are beginning to address the mistakes made through the exploration of single enantiomers and controlled-release preparations.
authors.affiliation: University of Minnesota, Center for Drug Design , 4-270 NHH 310 Church St. SE, Minneapolis, MN 55455 , USA +1 612 327 7630 ; vart0006@umn.edu.
authors.forename: Ashish P
authors.initials: AP
authors.lastname: Vartak
mesh_terms: D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D055808:Drug Discovery; D006801:Humans; D009292:Narcotic Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D009293:Opioid-Related Disorders / Q000188:drug therapy*
chemical_list: D009292:Narcotic Antagonists; D003000:Clonidine; C025655:lofexidine
keywords: adrenergic receptors; agonist; enantioselective synthesis; imidazole receptors; lofexidine; pharmacoeconomics; preclinical work