title: Metrifonate: update on a new antidementia agent.
abstract: OBJECTIVE
  To review preclinical and clinical studies of metrifonate, a cholinesterase inhibitor relevant to the treatment of Alzheimer's disease.
  
  
  METHODS
  English-language literature identified by MEDLINE using the term metrifonate was reviewed, and bibliography-sorted searches were conducted.
  
  
  RESULTS
  Metrifonate is an organophosphate cholinesterase inhibitor effective in the treatment of the cognitive symptoms of Alzheimer's disease and currently under review by the U.S. Food and Drug Administration. The active metabolite of metrifonate, 2,2-dimethyldichlorovinyl phosphate (DDVP), irreversibly inhibits the acetylcholinesterase enzyme. Although the elimination half-life of DDVP is 2-3 hours, the half-life of cholinesterase inhibition by DDVP is stable (26 days). Metrifonate can be administered once daily. Animal studies demonstrate its efficacy in enhancing memory in animals that have cholinergic deficits. Double-blind, placebo-controlled studies have shown the benefit of metrifonate compared with placebo in improving scores on the Clinical Global Impression of Change scale, the Alzheimer's Disease Assessment Scale-cognitive subscale, and the Neuropsychiatric Inventory.
  
  
  CONCLUSIONS
  Metrifonate is a useful addition to our limited armamentarium of agents helpful against the cognitive deficits of Alzheimer's disease.
authors.affiliation: Department of Neurology, University of California Los Angeles (UCLA) School of Medicine, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Ringman
authors.forename: J L
authors.initials: JL
authors.lastname: Cummings
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003072:Cognition Disorders / Q000188:drug therapy / Q000523:psychology; D004334:Drug Administration Schedule; D006801:Humans; D016239:MEDLINE; D010919:Placebos; D016896:Treatment Outcome; D014236:Trichlorfon / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D002800:Cholinesterase Inhibitors; D010919:Placebos; D014236:Trichlorfon