title: Drug development for the management of organophosphorus poisoning.
abstract: BACKGROUND
  The continuous application of organophosphate pesticides in developing countries, in addition to the remaining stock piles of chemical warfare nerve agents and their possible use is a significant threat to the public. Yet, today's options for a treatment of organophosphorus poisonings are still inadequate.
  
  
  METHODS
  This article provides a concise overview of current and future research trying to improve both prophylaxis and treatment of organophosphorus intoxications. The authors provide a summary of current oxime therapy and highlight several new concepts to overcome existing gaps. This overview of therapeutic options is accompanied by two sections on cyclodextrins, related compounds and bioscavengers, which may be used for either prophylaxis or treatment. For both groups, the authors review current drug design and screening approaches, the resulting developments and future challenges.
  
  
  CONCLUSIONS
  While the search for one multipotent oxime has been a fruitless endeavor, combination of multiple oximes with complemental and systemic reactivity appears as a valuable concept. Development of potential scavengers, be it cyclodextrins or bioscavengers, is still hampered by insufficient efficacy of these compounds. Future strategies will aim at improving their catalytic efficacy while minimizing immunogenicity.
authors.affiliation: Bundeswehr Institute of Pharmacology and Toxicology , Neuherbergstraße 11, D-80937 München , Germany +49 89 3168 2305 ; +49 89 3168 2333 ; timowille@bundeswehr.org.
authors.forename: Paul Wilhelm
authors.initials: PW
authors.lastname: Elsinghorst
authors.forename: Franz
authors.initials: F
authors.lastname: Worek
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.forename: Timo
authors.initials: T
authors.lastname: Wille
mesh_terms: D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D003505:Cyclodextrins / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D062025:Organophosphate Poisoning / Q000188:drug therapy*; D010091:Oximes / Q000627:therapeutic use
chemical_list: D000931:Antidotes; D003505:Cyclodextrins; D010091:Oximes